ORCID Profile
0000-0002-7761-5498
Current Organisation
Centro de Pesquisa em Medicina Tropical de Rondonia
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Publisher: American Chemical Society (ACS)
Date: 30-04-2021
Publisher: F1000 Research Ltd
Date: 14-04-2022
DOI: 10.12688/WELLCOMEOPENRES.17795.1
Abstract: This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 s les of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new s les contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published s les from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each s le has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr , dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.
Publisher: American Chemical Society (ACS)
Date: 20-04-2021
Publisher: Elsevier BV
Date: 12-2021
Publisher: Informa UK Limited
Date: 16-03-2016
DOI: 10.1080/08870446.2016.1146719
Abstract: The current article details a position statement and recommendations for future research and practice on planning and implementation intentions in health contexts endorsed by the Synergy Expert Group. The group comprised world-leading researchers in health and social psychology and behavioural medicine who convened to discuss priority issues in planning interventions in health contexts and develop a set of recommendations for future research and practice. The expert group adopted a nominal groups approach and voting system to elicit and structure priority issues in planning interventions and implementation intentions research. Forty-two priority issues identified in initial discussions were further condensed to 18 key issues, including definitions of planning and implementation intentions and 17 priority research areas. Each issue was subjected to voting for consensus among group members and formed the basis of the position statement and recommendations. Specifically, the expert group endorsed statements and recommendations in the following areas: generic definition of planning and specific definition of implementation intentions, recommendations for better testing of mechanisms, guidance on testing the effects of moderators of planning interventions, recommendations on the social aspects of planning interventions, identification of the preconditions that moderate effectiveness of planning interventions and recommendations for research on how people use plans.
Publisher: Springer Science and Business Media LLC
Date: 08-2019
Publisher: Cold Spring Harbor Laboratory
Date: 14-05-2021
DOI: 10.1101/2021.05.12.443866
Abstract: Drug resistance and a dire lack of transmission-blocking antimalarials h er malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class acetyl-CoA synthetase (ACS) inhibitor to enter preclinical development. Our studies demonstrated attractive drug-like properties and in vivo efficacy in a humanized mouse model of Plasmodium falciparum infection. The compound showed exceptional in vitro activity against P. falciparum and P. vivax clinical isolates, and potently blocked P. falciparum transmission to Anopheles mosquitoes. Genetic and biochemical studies identified ACS as the target of the MMV693183-derived antimetabolite, CoA-MMV693183. MMV693183 was well adsorbed after oral administration in mice, rats and dogs. Pharmacokinetic – pharmacodynamic modelling predicted that a single 30 mg oral dose is sufficient to cure a malaria infection in humans. In conclusion, the ACS-targeting compound MMV693183 represents a promising addition to the portfolio of antimalarials in (pre)clinical development with a novel mode of action for the treatment of malaria and blocking transmission.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2022
DOI: 10.1038/S41467-022-29688-5
Abstract: Drug resistance and a dire lack of transmission-blocking antimalarials h er malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class acetyl-CoA synthetase (AcAS) inhibitor to enter preclinical development. Our studies demonstrate attractive drug-like properties and in vivo efficacy in a humanized mouse model of Plasmodium falciparum infection. The compound shows single digit nanomolar in vitro activity against P. falciparum and P. vivax clinical isolates, and potently blocks P. falciparum transmission to Anopheles mosquitoes. Genetic and biochemical studies identify AcAS as the target of the MMV693183-derived antimetabolite, CoA-MMV693183. Pharmacokinetic-pharmacodynamic modelling predict that a single 30 mg oral dose is sufficient to cure a malaria infection in humans. Toxicology studies in rats indicate a 30-fold safety margin in relation to the predicted human efficacious exposure. In conclusion, MMV693183 represents a promising candidate for further (pre)clinical development with a novel mode of action for treatment of malaria and blocking transmission.
Publisher: Springer Science and Business Media LLC
Date: 26-05-2021
DOI: 10.1038/S41467-021-23422-3
Abstract: Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic ersity of circulating parasite populations is not well described. Determinants of antimalarial drug susceptibility for P. vivax in the region have not been characterised. Our genomic analysis of global P. vivax ( n = 558) establishes South Asian isolates ( n = 92) as a distinct subpopulation, which shares ancestry with some East African and South East Asian parasites. Signals of positive selection are linked to drug resistance-associated loci including pvkelch10, pvmrp1, pvdhfr and pvdhps , and two loci linked to P. vivax invasion of reticulocytes, pvrbp1a and pvrbp1b . Significant identity-by-descent was found in extended chromosome regions common to P. vivax from India and Ethiopia, including the pvdbp gene associated with Duffy blood group binding. Our investigation provides new understanding of global P. vivax population structure and genomic ersity, and genetic evidence of recent directional selection in this important human pathogen.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Springer Science and Business Media LLC
Date: 23-12-2022
DOI: 10.1038/S42003-022-04352-2
Abstract: Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection’s country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control programs.
Publisher: Cold Spring Harbor Laboratory
Date: 13-12-2022
DOI: 10.1101/2022.12.11.22282391
Abstract: Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency. Data from similar clinical studies evaluating the performance of the STANDARD ™ G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD ™ G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%–100%) for G6PD deficient cases with % activity and 77% (95% CI 66.8%– 85.4%) for females with intermediate activity between 30%–70%. Specificity was 98.1% (95% CI 97.6%–98.5%) and 92.8% (95% CI 91.6%–93.9%) for G6PD deficient in iduals and intermediate females, respectively. The majority (12/20) of G6PD intermediate females with false normal results had activity levels % on the reference assay. Negative predictive values for females with G6PD activity % was 99.6% (95% CI 99.1%–99.8%) on capillary specimens. Test sensitivity among 396 P. vivax malaria cases was 100% (69.2%–100.0%) for both deficient and intermediate cases. In the study population, a high proportion of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, the majority cases would receive the correct medication and no true G6PD deficient cases would be treated inappropriately. The STANDARD G6PD Test enables safe access to drugs which are contraindicated for in iduals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.
Publisher: Public Library of Science (PLoS)
Date: 04-10-2019
No related grants have been discovered for Dhelio Pereira.