A5011546643- Malaria Research and Control
- Mosquito-borne diseases and control
- vaccines and immunoinformatics approaches
- HIV Research and Treatment
- Complement system in diseases
- Parasites and Host Interactions
- Computational Drug Discovery Methods
- Trypanosoma species research and implications
- Microbial infections and disease research
- Evolution and Genetic Dynamics
- Invertebrate Immune Response Mechanisms
- Aquaculture disease management and microbiota
- Helminth infection and control
- Drug-Induced Hepatotoxicity and Protection
- Research on Leishmaniasis Studies
- Drug Transport and Resistance Mechanisms
- Genomics and Phylogenetic Studies
- Vector-borne infectious diseases
- Diverse Scientific Research Studies
- Parasite Biology and Host Interactions
- Hemoglobinopathies and Related Disorders
- Machine Learning in Bioinformatics
- COVID-19 epidemiological studies
- Virology and Viral Diseases
- Hepatitis B Virus Studies
University of Maryland, Baltimore
2016-2025
Université Félix Houphouët-Boigny
2023
Myanmar Oxford Clinical Research Unit
2023
University of Baltimore
2015-2023
Centre for Global Health Research
2017
Howard Hughes Medical Institute
2010-2015
National Institutes of Health
2014
Blood-stage malaria vaccines are intended to prevent clinical disease. The vaccine FMP2.1/AS02(A), a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown have immunogenicity and acceptable safety in Malian adults children.In double-blind, randomized trial, we immunized 400 children with either or control (rabies) followed them for 6 months. primary end point was malaria, defined as fever at least 2500 parasites...
The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for elimination. Identification the genetic basis resistance would provide tools molecular surveillance, aiding efforts to contain resistance. Clinical trials artesunate efficacy were conducted Bangladesh, northwestern Thailand near Myanmar border, and at two sites Cambodia. Parasites collected from trial participants genotyped 8,079 single nucleotide polymorphisms (SNPs)...
Abstract The widely used antimalarial combination therapy dihydroartemisinin + piperaquine (DHA PPQ) has failed in Cambodia. Here, we perform a genomic analysis that reveals rapid increase the prevalence of novel mutations Plasmodium falciparum chloroquine resistance transporter PfCRT following DHA PPQ implementation. These occur parasites harboring K13 C580Y artemisinin marker. By introducing into sensitive Dd2 or removing them from resistant Cambodian isolates, show H97Y, F145I, M343L,...
The spread of drug-resistant Plasmodium falciparum malaria has been a major impediment to control and threatens prospects for elimination. We recently demonstrated the return chloroquine-susceptible in Malawi after chloroquine use was abandoned. In this study, we trace origins chloroquine-resistant parasites by sequencing P. resistance transporter gene (pfcrt) genotyping microsatellites flanking isolates from infections that occurred 1992 through 2005. Malaria 2005 harbored expected...
Artemisinin resistance in Plasmodium falciparum has emerged Southeast Asia and poses a threat to malaria control elimination. Mutations P. gene encoding kelch protein on chromosome 13 have been associated with delayed parasite clearance following artemisinin treatment elsewhere the region, but not yet China.Therapeutic efficacy studies of artesunate dihydroartemisinin-piperaquine were conducted from 2009 2012 Yunnan Province China near border Myanmar. K13 mutations genotyped by capillary...
Amplified copy number in the plasmepsin II/III genes within Plasmodium falciparum has been associated with decreased sensitivity to piperaquine. To examine this association and test whether additional loci might also contribute, we performed a genome-wide study of ex vivo P. susceptibility DNA from 183 samples collected primarily Cambodia was genotyped at 33716 single nucleotide polymorphisms (SNPs). Linear mixed models random forests were used estimate associations between parasite...
Artemisinin-resistant Plasmodium falciparum malaria has been documented in southeast Asia and may already be spreading that region. Molecular markers are important tools for monitoring the spread of antimalarial drug resistance. Recently, single-nucleotide polymorphisms (SNPs) PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to associated with artemisinin resistance vivo vitro . The prevalence role K13-propeller mutations poorly known sub-Saharan Africa. genotyped by direct...
Background. The return of chloroquine-sensitive Plasmodium falciparum to the limited area Blantyre, Malawi, has been well demonstrated in several studies. Methods. To characterize chloroquine susceptibility over a wide geographic area, infants and children aged 6–59 months were selected using 2-stage cluster sampling 8 Malawian districts. Pyrosequencing pfcrt gene codon 76 region was performed for with asexual parasitemia. Results. Of 7145 children, 1150 had microscopic parasitemia,...
Abstract Malaria genomic surveillance often estimates parasite genetic relatedness using metrics such as Identity-By-Decent (IBD), yet strong positive selection stemming from antimalarial drug resistance or other interventions may bias IBD-based estimates. In this study, we use simulations, a true IBD inference algorithm, and empirical data sets different malaria transmission settings to investigate the extent of explore potential correction strategies. We analyze whole genome sequence...
Genomic surveillance is crucial for identifying at-risk populations targeted malaria control and elimination. Identity-by-descent (IBD) increasingly being used in Plasmodium population genomics to estimate genetic relatedness, effective size ( N e ), structure, signals of positive selection. Despite its potential, a thorough evaluation IBD segment detection tools species with high recombination rates, such as P. falciparum , remains absent. Here, we perform comprehensive benchmarking callers...
The disappointing efficacy of blood-stage malaria vaccines may be explained in part by allele-specific immune responses that are directed against polymorphic epitopes on antigens. FMP2.1/AS02A, a candidate vaccine based apical membrane antigen 1 (AMA1) from the 3D7 strain Plasmodium falciparum, had clinical phase II trial Malian children. We assessed cross-protective and inferred which amino acid positions AMA1 were targets protective responses. FMP2.1/AS02A highest alleles identical to...
Cambodia's first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistant Plasmodium falciparum malaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying for ex vivo susceptibility molecular markers guide the selection of an effective alternative DHA-PPQ. Over last 3 study years, PPQ...
Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation these results and understanding their relevance vaccine efficacy hampered by lack knowledge on genetic differences between...
Abstract Background Extensive genetic diversity in vaccine antigens may contribute to the lack of efficacy blood stage malaria vaccines. Apical membrane antigen-1 (AMA1) is a leading candidate with extreme diversity, potentially limiting its against infection and disease caused by Plasmodium falciparum parasites diverse forms AMA1. Methods Three hundred Malian children participated Phase 2 clinical trial bivalent that found no protective efficacy. The consists recombinant AMA1 based on 3D7...
Estimates of Plasmodium falciparum migration may inform strategies for malaria elimination. Here we elucidate fine-scale parasite population structure and infer recent across Southeast Asia using identity-by-descent (IBD) approaches based on genome-wide single nucleotide polymorphisms called in 1722 samples from 54 districts. IBD estimates are consistent with isolation-by-distance. We observe greater sharing larger segments between artemisinin-resistant parasites versus sensitive parasites,...
Genomic surveillance is crucial for identifying at-risk populations targeted malaria control and elimination. Identity-by-descent (IBD) increasingly being used in Plasmodium population genomics to estimate genetic relatedness, effective size ( N e ), structure, signals of positive selection. Despite its potential, a thorough evaluation IBD segment detection tools species with high recombination rates, such as P. falciparum , remains absent. Here, we perform comprehensive benchmarking callers...
The repetitive interspersed family (rif) and subtelomeric variable open reading frames (stevor) are highly diverse multi-gene families in the malaria parasite Plasmodium falciparum. Embedded on surface of infected erythrocytes, RIFIN STEVOR proteins involved cytoadherence immune evasion, but extent family-wide sequence diversity across strains has yet to be comprehensively investigated light improved resolution genome sequences. Using a k-mer frequency approach, we analyzed long-read genomic...