02296nas a2200241   4500008004100000022001400041245011200055210006900167260000800236300001100244490000800255520148600263653001801749653002401767653001201791653001501803653001501818100002501833700001901858700002801877700001701905856013201922       2022                        eng d  a0166-685100aProfiling of metabolic alterations in mice infected with malaria parasites via high-resolution metabolomics0 aProfiling of metabolic alterations in mice infected with malaria  cNOV  a1115250 v2523 a<p>
	Background: Malaria infection can result in distinct clinical outcomes from asymptomatic to severe. The association between patho-physiological changes and molecular changes in the host, and their correlation with severity of malaria progression is not fully understood. Methods: In this study, we addressed mass spectrometry-based temporal profiling of serum metabolite levels from mice infected with Plasmodium berhgei (strain ANKA). Results: We show global perturbations and identify changes in specific metabolites in correlation with disease progression. While metabolome-wide changes were apparent in late-stage malaria, a subset of metabolites exhibited highly correlated changes with disease progression. These metabolites changed early on following infection and either continued or maintained the change as mice developed severe disease. Some of these have the potential to be sentinel metabolites for severe malaria. Moreover, glycolytic metabolites, purine nucleotide precursors, tryptophan and its bioactive derivatives were many fold decreased in late-stage disease. Interestingly, uric acid, a metabolic waste reported to be elevated in severe human malaria, increased with disease progression, and subsequently appears to be detoxified into allantoin. This detoxification mechanism is absent in humans as they lack the enzyme uricase. Conclusions: We have identified candidate marker metabolites that may be of relevance in the context of human malaria.</p>
10aHost response10aInfectious diseases10amalaria10ametabolite10aPlasmodium1 aChhibber-Goel, Jyoti1 aShukla, Anurag1 aShanmugam, Dhanasekaran1 aSharma, Amit  uhttps://library.ncl.res.in/content/profiling-metabolic-alterations-mice-infected-malaria-parasites-high-resolution-metabolomics03461nas a2200301   4500008004100000022001400041245012200055210006900177260000800246300001200254490000700266520249900273653002002772653001202792653002002804653001802824653001202842100002102854700001902875700001902894700001702913700002102930700002202951700001602973700001702989700002803006856012503034       2026                        eng d  a2328-895700aTargeted genomic surveillance unveils genetic variations linked to regional malaria drug resistance dynamics in India0 aTargeted genomic surveillance unveils genetic variations linked   cMAR  aofag1060 v133 a<p>
	Background India has made substantial progress in reducing Plasmodium falciparum malaria cases and has set a target to eliminate malaria by 2030. Although artemisinin-based combination therapy (ACT) treatment remains effective, tracking regional differences in genetic variants associated with antimalarial resistance is required for effective drug policy implementation.Methods We analyzed 238 P. falciparum clinical samples from 6 Indian states by sequencing 15 parasite genes associated with reduced drug effectiveness. The method involved nanopore sequencing of target gene amplicons derived from dried blood spots using a highly-sensitive PfMDR15 surveillance panel.Results India's historical policy of artesunate-sulfadoxine-pyrimethamine in central India and artemether-lumefantrine in the Northeast has shaped contrasting resistance profiles. In the Northeast, chloroquine resistance persisted at high frequency (Pfcrt K76T and CVIET haplotype; Pfaat1 S258L), alongside quintuple and sextuple Pfdhfr-Pfdhps haplotypes conferring complete sulfadoxine-pyrimethamine resistance. Central India showed variable chloroquine resistance (parasites largely retained wild-type Pfcrt) and emerging lumefantrine tolerance (Pfmdr1 Y184F, Pfaat1 S258L). Interestingly, Delhi (Central India) parasites resembled profiles from the distant Northeast, which borders South East Asia. The detection of Pfaat1 S258L, previously reported only from Africa and associated with reduced lumefantrine susceptibility, suggests convergent evolution under ACT partner-drug pressure. No WHO-validated Pfk13 artemisinin resistance mutations were detected, supporting continued efficacy of ACT.Conclusions India's resistance landscape is fragmented, with signals of expanding lumefantrine tolerance and importation or evolution of globally relevant mutations. These findings highlight the importance of integrating molecular genomic surveillance into malaria control policy to monitor and protect ACT effectiveness and advance malaria elimination. Monitoring of drug resistance associated mutations in P. falciparum parasites is critical for effective drug treatment. We have demonstrated the use of a scalable genomic surveillance protocol for tracking drug resistance linked mutations in parasite genes from clinical isolates in India. The study suggests extensive regional diversity in antimalarial resistance profiles and provides the first hint of possible emergence of lumefantrine tolerance in India.</p>
10adrug resistance10amalaria10aOxford nanopore10aP. falciparum10apfMDR151 aKhilari, Ajinkya1 aSharma, Shweta1 aBajpai, Manali1 aViswan, Anju1 aChaturvedi, Rini1 aMirdha, Bijay, R.1 aRahi, Manju1 aSharma, Amit1 aShanmugam, Dhanasekaran  uhttps://library.ncl.res.in/content/targeted-genomic-surveillance-unveils-genetic-variations-linked-regional-malaria-drug