A5007312956- Malaria Research and Control
- Mosquito-borne diseases and control
- Complement system in diseases
- Parasites and Host Interactions
- HIV Research and Treatment
- Fungal and yeast genetics research
- Evolution and Genetic Dynamics
- Erythrocyte Function and Pathophysiology
- Parasite Biology and Host Interactions
- Genetic diversity and population structure
- Vector-borne infectious diseases
- Antifungal resistance and susceptibility
- Blood groups and transfusion
- Toxoplasma gondii Research Studies
- Clostridium difficile and Clostridium perfringens research
- Metabolism and Genetic Disorders
- Pharmacogenetics and Drug Metabolism
- Plant-derived Lignans Synthesis and Bioactivity
- HIV/AIDS drug development and treatment
- Catalytic Alkyne Reactions
- Pneumocystis jirovecii pneumonia detection and treatment
- Research on Leishmaniasis Studies
- Mitochondrial Function and Pathology
- Otolaryngology and Infectious Diseases
- Hemoglobinopathies and Related Disorders
Case Western Reserve University
2008-2021
Center for Global Health
2009-2021
Wake Forest University
2005
National Institutes of Health
1998-2003
National Institute of Allergy and Infectious Diseases
1999-2000
Malaria therapy, experimental, and epidemiological studies have shown that erythrocyte Duffy blood group-negative people, largely of African ancestry, are resistant to Plasmodium vivax infection. These findings established a paradigm the antigen is required for P. invasion. endemic in Madagascar, where admixture Duffy-negative Duffy-positive populations diverse ethnic backgrounds has occurred over 2 millennia. There, we investigated susceptibility blood-stage infection disease association...
Background Plasmodium vivax invasion requires interaction between the human Duffy antigen on surface of erythrocytes and P. binding protein (PvDBP) expressed by parasite. Given that Duffy-negative individuals are resistant heterozygotes show reduced susceptibility to blood-stage infection, we hypothesized antibodies directed against region two (PvDBPII) would inhibit erythrocytes. Methods Findings Using a recombinant (rPvDBPII), polyclonal were generated from immunized rabbits affinity...
Ivo Mueller and colleagues examined the association of Southeast Asian ovalocytosis with Plasmodium vivax infection by genotyping 1975 children enrolled in three independent epidemiological studies conducted Madang area Papua New Guinea assessing P. disease children.
Plasmodium vivax (Pv) is a major cause of human malaria and increasing in public health importance compared with falciparum malaria. Pv unique among malarias that invasion erythrocytes almost solely dependent on the red cell's surface receptor, known as Duffy blood-group antigen (Fy). Fy an important minor has two immunologically distinct alleles, referred to or b , resulting from single-point mutation. This mutation occurs within binding domain parasite's cell ligand. Whether this...
Improving strategies for diagnosing infection by the four human Plasmodium species parasites is important as field-based epidemiologic and clinical studies focused on malaria become more ambitious. Expectations diagnostic assays include rapid processing with minimal expertise, very high specificity sensitivity, quantitative evaluation of parasitemia to be delivered at a low cost. Toward fulfilling many these expectations, we have developed post-polymerase chain reaction (PCR)/ligase...
During intra-erythrocytic development, malaria trophozoites digest hemoglobin, which leads to parasite growth and asexual replication while accumulating toxic heme. To avoid death, the synthesizes insoluble hemozoin crystals in digestive vacuole through polymerization of beta-hematin dimers. In process, heme is converted a high-spin ferriheme whose magnetic properties were studied as early 1936 by Pauling et al. Here, magnetophoretic cell motion analysis, we provide evidence for graduated...
Abstract The complex life cycle of Plasmodium falciparum (Pf) makes it difficult to limit infections and reduce the risk severe malaria. Improved understanding Pf blood‐stage growth development would provide new opportunities evaluate interfere with successful completion parasite's cycle. Cultured blood stage was incubated Hoechst 33342 (HO) thiazole orange (TO) stain DNA total nucleic acids, respectively. Correlated HO TO fluorescence emissions were then measured by flow cytometry. Complex...
The number of available and effective antimalarial drugs is quickly dwindling. This mainly because a drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, others, have led to widespread resistance all known classes compounds. Unfortunately, parasites started exhibit some level Southeast Asia even the most recently introduced class drugs, artemisinins. While there much need, development pipeline remains woefully thin, with little chemical diversity,...
Abstract Natural infection of SARS-CoV-2 in humans leads to the development a strong neutralizing antibody response, however immunodominant targets polyclonal response are still unknown. Here, we functionally define role spike plays as target human response. In this study, identify protein subunits that contain antigenic determinants and examine neutralization capacity sera from cohort patients tested qRT-PCR-positive for SARS-CoV-2. Using an ELISA format, assessed binding subunit 1 (S1), 2...
High-level azole resistance in the Darlington strain of Candida albicans was investigated by gene replacement C. and expression Saccharomyces cerevisiae. We sequenced ERG11 gene, which encodes sterol C(14)alpha-demethylase, from our copy strain. Both alleles contained histidine for tyrosine substitution at position 132 (Y132H) reported others, but we also found a threonine-for-isoleucine (I471T) not previously ERG11. The encoded I471T change amino acids conferred when overexpressed alone...
Abstract Background Aggregated haemozoin crystals within malaria-infected erythrocytes confer susceptibility of parasitized cells to a magnetic field. Here the utility this method for diagnosis human malaria is evaluated in malaria-endemic region Papua New Guinea (PNG). Methods and findings Individuals with Plasmodium falciparum symptoms (n = 55) provided samples conventional blood smear (CBS) deposition microscopy (MDM) diagnosis. Standard Giemsa staining light was performed evaluate all...
Abstract The rapid increase in azole resistance during treatment of patients infected with Candida glabrata may be due to increased efflux mediated by ABC transporters, as occurs expression PDR5 Saccharomyces cerevisiae . Two known C. homologues influencing susceptibility are PDH1 ( CgCDR2 ) and CgCDR1 Disruption a cgcdr1::ura3 strain rhodamine 6G, cycloheximide chloramphenicol, also 6G accumulation, all properties pdr5 null mutants. Overexpression S. complemented the mutation reversing...
Abstract Malaria, caused by protozoan Plasmodium parasites, kills ∼800,000 people each year. Exact figures are uncertain because presumptive diagnoses often made without identifying parasites in patients' blood either microscopy, using Giemsa's century‐old stain, or simpler tests that ultimately dependent on microscopy for quality control. Microscopy itself relies trained observers' ability to detect subtle morphological features of parasitized red cells, only a few which may be present...
Some hypotheses for the evolution of sex focus on adaptation to changing or heterogeneous environments, but these have rarely been tested. We tested advantages and increased mutation rates in yeast strains two contrasting environments: a standard relatively homogeneous laboratory environment minimal medium test tubes, variable mouse brain experienced by pathogenic strains. Evolving populations were founded as equal mixtures sexual obligately asexual genotypes. In sexuals, cycles sporulation,...
An antimalarial screen for plants collected from Papua New Guinea identified an extract of Horsfieldia spicata as having activity. Isolation the active constituents led to identification two new compounds: myristicyclins A (1) and B (2). Both compounds are procyanidin-like congeners myristinins lacking a pendant aromatic ring. Myristicyclin was found inhibit ring, trophozoite, schizont stages Plasmodium falciparum at similar concentrations in mid-μM range.
Plasmodium vivax is the most prevalent human malaria parasite and likely to increase proportionally as control efforts more rapidly impact prevalence of falciparum. Despite prominence P. a major pathogen, qualifies neglected under-studied tropical disease. Significant challenges bringing into laboratory, particularly capacity for long-term propagation well-characterized strains, have limited study this parasite's red blood cell (RBC) invasion mechanism, blood-stage development, gene...
Zika virus (ZIKV) is a significant public health concern due to the pathogen’s ability be transmitted by either mosquito bite or sexual transmission, allowing spread occur throughout world. The potential consequences of ZIKV infection human health, specifically neonates, necessitates development safe and effective vaccine. Here, we developed an intranasal vaccine based upon replication-deficient adenovirus serotype 5 (hAd5) expressing pre-membrane envelope protein (hAd5-ZKV). hAd5-ZKV able...
Malaria remains widespread throughout the tropics and is a burden to estimated 3.5 billion people who are exposed annually. The lack of fast accurate diagnostic method contributes preventable malaria deaths its continued transmission. In many areas diagnosis made solely based on clinical presentation. Current methods for take more than 20 minutes from time blood drawn frequently inaccurate. introduction an that can provide result in less 1 minute would allow screening treatment endemic...
Malaria and schistosomiasis coinfections are common, chronic has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria controversial due lack appropriately controlled human studies relevant animal models. To examine this interaction, we conducted a randomized study using baboon (Papio anubis) to analyze effect on severe Two groups baboons (n = 8 each) control group 3) were infected with 500 Schistosoma mansoni cercariae. At 14 15 weeks...
Conventional malaria parasite detection methods, such as rapid diagnostic tests (RDT) and light microscopy (LM), are not sensitive enough to detect low level parasites identification of gametocytes in the peripheral blood. A modified laboratory prototype, Magnetic Deposition Microscopy (MDM) was developed increase sub-microscopic parasitaemia estimation density asymptomatic school children.Blood samples were collected from 303 children seven villages Bagamoyo district Tanzania. Participants...