A5080134164- Malaria Research and Control
- Mosquito-borne diseases and control
- Parasites and Host Interactions
- Computational Drug Discovery Methods
- Aquaculture disease management and microbiota
- Parasite Biology and Host Interactions
- Invertebrate Immune Response Mechanisms
- Evolution and Genetic Dynamics
- HIV Research and Treatment
- Vector-borne infectious diseases
- Trypanosoma species research and implications
- HIV/AIDS drug development and treatment
- Genetic diversity and population structure
- African history and culture analysis
- vaccines and immunoinformatics approaches
- Travel-related health issues
- Global Maritime and Colonial Histories
- Genetics, Bioinformatics, and Biomedical Research
- Complement system in diseases
- Drug-Induced Hepatotoxicity and Protection
- Vibrio bacteria research studies
- Research on Leishmaniasis Studies
- Drug Transport and Resistance Mechanisms
- Microbial infections and disease research
- Digital Imaging for Blood Diseases
Harvard University
2015-2024
Simmons University
2015-2024
Broad Institute
2014-2023
Boston University
2008-2022
Harvard University Press
2011-2020
National Office for Sanitation of Senegal
2020
Yale University
2020
Cheikh Anta Diop University
2020
Ministère de la Santé Publique
2020
Massachusetts Institute of Technology
2013-2017
The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical severe malaria disease in infants children. We investigated whether was specific to certain parasite genotypes at locus.We used polymerase chain reaction-based next-generation sequencing DNA extracted from samples 4985 participants survey polymorphisms. evaluated effect that polymorphic positions haplotypic regions within had on first episodes 1 year after...
Significance Traditional methods for estimating malaria transmission based on mosquito sampling are not standardized and unavailable in many countries sub-Saharan Africa. Such studies especially difficult to implement when is low, low the goal of elimination. Malaria-control efforts Senegal have resulted changes population genomics evidenced by increased allele sharing among parasite genomes, often including genomic identity between independently sampled parasites. Fitting an epidemiological...
Abstract Background Single nucleotide polymorphism (SNP) genotyping provides the means to develop a practical, rapid, inexpensive assay that will uniquely identify any Plasmodium falciparum parasite using small amount of DNA. Such an could be used distinguish recrudescence from re-infection in drug trials, monitor frequency and distribution specific parasites patient population undergoing treatment or vaccine challenge, for tracking samples determining purity isolates laboratory during...
Genetic variability of Plasmodium falciparum underlies its transmission success and thwarts efforts to control disease caused by this parasite. variation in antigenic, drug resistance, pathogenesis determinants is abundant, consistent with an ancient origin P. , whereas DNA at silent (synonymous) sites coding sequences appears virtually absent, a recent the To resolve paradox, we analyzed introns demonstrated that these are deficient single-nucleotide polymorphisms, as synonymous regions....
Discovering novel genes involved in immune evasion and drug resistance the human malaria parasite, Plasmodium falciparum, is of critical importance to global health. Such knowledge may assist development new effective vaccines appropriate use antimalarial drugs. By performing a full-genome scan allelic variability 14 field laboratory strains P. we comprehensively identified ≈500 evolving at higher than neutral rates. The majority most variable have paralogs within falciparum genome be...
Drug resistance is an obstacle to global malaria control, as evidenced by the recent emergence and rapid spread of delayed artemisinin (ART) clearance mutant forms PfKelch13 protein in Southeast Asia. Identifying genetic determinants ART African-derived parasites important for surveillance understanding mechanism resistance. In this study, we carried out long-term vitro selection two recently isolated West African (from Pikine Thiès, Senegal) with increasing concentrations dihydroartemisinin...
Mounting evidence suggests a major role for epigenetic feedback in Plasmodium falciparum transcriptional regulation. Long non-coding RNAs (lncRNAs) have recently emerged as new paradigm remodeling. We therefore set out to investigate putative roles lncRNAs P. used high-resolution DNA tiling microarray survey activity across 22.6% of the strain 3D7 genome. identified 872 protein-coding genes and 60 under developmental regulation during parasite's pathogenic human blood stage. Further...
Background: Although thousands of clinical isolates Plasmodium falciparum are being sequenced and analysed by short read technology, the data do not resolve highly variable subtelomeric regions genomes that contain polymorphic gene families involved in immune evasion pathogenesis. There is also no current standard definition boundaries these regions. Methods: Using long-read sequence (Pacific Biosciences SMRT technology), we assembled annotated 15 P. isolates, ten which newly cultured...
Plasmodium vivax, one of the five species parasites that cause human malaria, is responsible for 25–40% malaria cases worldwide. Malaria global elimination efforts will benefit from accurate and effective genotyping tools provide insight into population genetics diversity this parasite. The recent sequencing P. vivax isolates South America, Africa, Asia presents a new opportunity by uncovering thousands novel single nucleotide polymorphisms (SNPs). Genotyping selection these SNPs provides...
Significance This study addresses the evolutionary dynamics of antimalarial drug resistance after changes in use. We show that chloroquine Plasmodium falciparum from French Guiana was lost sustained removal, whereas marker PfCRT K76T remained fixed parasite population. phenotypic reversion caused by acquisition a single additional C350R substitution PfCRT. genetic change also impaired susceptibility to piperaquine, suggesting piperaquine pressure drove expansion this allele. These findings...
Artemisinin resistance is associated with delayed parasite clearance half-life in vivo and correlates ring-stage survival under dihydroartemisinin vitro. Both phenotypes are mutations the PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin emerging piperaquine Southeast Asia show that combination therapy, such as dihydroartemisinin–piperaquine, losing clinical effectiveness, prompting investigation drug mechanisms development strategies to surmount anti-malarial resistance....
Using parasite genotyping tools, we screened patients with mild uncomplicated malaria seeking treatment at a clinic in Thiès, Senegal, from 2006 to 2011. We identified growing frequency of infections caused by genetically identical strains, coincident increased deployment control interventions and decreased deaths. Parasite genotypes some cases persisted clonally across dry seasons. The increase strains corresponded decrease the probability multiple infections. Further, these observations...
We have adapted a solution hybrid selection protocol to enrich pathogen DNA in clinical samples dominated by human genetic material. Using mock mixtures of and Plasmodium falciparum malaria parasite as well from infected patients, we demonstrate an average approximately 40-fold enrichment after selection. This approach will enable efficient genome sequencing pathogens samples, endosymbiotic organisms such Wolbachia that live inside diverse metazoan phyla.
Through rapid genetic adaptation and natural selection, the Plasmodium falciparum parasite—the deadliest of those that cause malaria—is able to develop resistance antimalarial drugs, thwarting present efforts control it. Genome-wide association studies (GWAS) provide a critical hypothesis-generating tool for understanding how this occurs. However, in P. , limited amount linkage disequilibrium hinders power traditional array-based GWAS. Here, we demonstrate feasibility improvements gained by...
Multidrug resistant Plasmodium falciparum in Southeast Asia endangers regional malaria elimination and threatens to spread other endemic areas. Understanding mechanisms of piperaquine (PPQ) resistance is crucial for tracking its emergence spread, develop effective strategies overcoming it. Here we analyze a mechanism PPQ Cambodian parasites. Isolates exhibit bimodal dose-response curve when exposed PPQ, with the area under quantifying their survival vitro. Increased copy number plasmepsin II...
Molecular epidemiology leverages genetic information to study the risk factors that affect frequency and distribution of malaria cases. This article describes molecular epidemiologic investigations currently being carried out by International Centers Excellence for Malaria Research (ICEMR) network in a variety malaria-endemic settings. First, we discuss various novel approaches understand incidence gametocytemia, focusing on Plasmodium falciparum vivax. Second, describe compare different...
Abstract Background The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts study in P. have begun elucidate the demographic history of species, well patterns population structure linkage disequilibrium within genome. Such studies will be greatly enhanced by new genomic tools recent large-scale map variation. To that end, we developed high throughput single nucleotide polymorphism (SNP)...
The identification of genetic changes that confer drug resistance or other phenotypic in pathogens can help optimize treatment strategies, support the development new therapeutic agents, and provide information about likely function genes. Elucidating mechanisms also assist identifying mode action uncharacterized but potent antimalarial compounds identified high-throughput chemical screening campaigns against Plasmodium falciparum.Here we show tiling microarrays detect de novo a large...
The Plasmodium falciparum parasite's ability to adapt environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden public health. Understanding genetic basis of these adaptations is critical intervening successfully against malaria. To that end, we created a high-density genotyping array assays over 17,000 single nucleotide polymorphisms (∼1 SNP/kb), applied it 57 culture-adapted parasites from three continents. We characterized...
Complex malaria infections are defined as those containing more than one genetically distinct lineage of Plasmodium parasite. Complexity infection (COI) is a useful parameter to estimate from patient blood samples because it associated with clinical outcome, epidemiology and disease transmission rate. This manuscript describes method for estimating COI using likelihood, called COIL, panel bi-allelic genotyping assays. COIL assumes that parasite lineages in complex unrelated genotyped loci do...
Significance Genomic sequences of 159 isolates the malaria parasite Plasmodium falciparum exhibited highly unusual patterns single-nucleotide polymorphism. We hypothesized that these might result from repeated bottlenecks in host–vector and vector–host transmission as well intense competition between parasites within a single host. Computer simulations life cycle recapitulated polymorphism observed. In classical Wright–Fisher model population genetics, random changes gene frequency caused by...
Identifying the source of resurgent parasites is paramount to a strategic, successful intervention for malaria elimination. Although incidence in Panama low, recent outbreak resulted 6-fold increase reported cases. We hypothesized that sampled from this epidemic might be related and exhibit clonal population structure. tested genetic relatedness parasites, using informative single-nucleotide polymorphisms drug resistance loci. found were clustered into 3 subpopulations Colombia. Two clusters...