Immunology and Infectious Disease Commons^™

Msphere Of Influence: Autoantibodies During Malaria—A Historical Observation Taking The Modern Spotlight, Juan Rivera-Correa

Publications and Research

Juan Rivera-Correa works in the field of immunology of tropical infectious diseases, focusing on the role of autoimmune responses in malaria. In this mSphere of Influence article, he discusses the papers by Rosenberg and Daniel-Ribeiro, which were two of the first papers to report the presence of autoantibodies in malaria patients, changing the paradigm and blurring the line between autoimmune disorders and infectious diseases.

Repurposing Cyclin-Dependent Kinase Inhibitors For The Discovery Of Novel Antiplasmodial Compounds, Ritam Bhowmik

Honors Undergraduate Theses

Malaria remains a major global health burden with over 282 million cases annually and rising resistance to artemisinin-based combination therapies. Plasmodium falciparum, the most lethal malaria parasite species in humans, relies on tightly regulated cell cycle progression during replication within red blood cells. Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell division and transcription, and several CDK-like enzymes in P. falciparum, including Pfmrk and PfPK6, are essential for parasite growth and structurally distinct from human kinases. This study evaluated whether commercially available human CDK inhibitors (CDKIs) targeting cancer pathways could be repurposed as novel antimalarial compounds. A library of …

A Randomized Controlled Trial Combining House Screening And Insecticide-Treated Nets Reduces Malaria Transmission In Northwestern Ethiopia, Aklilu K. Belay, Abebe Asale, Catherine L. Sole, Abdullahi A. Yusuf, Baldwyn Torto, Zewdu Abro, Menale Kassie, Clifford M. Mutero, David P. Tchouassi

All Peer-Reviewed Publications

House screening (HS) of doors, eaves, and windows using wire-mesh has demonstrated potential in the integrated vector management of malaria. However, limited epidemiological data are available to guide its implementation across different ecological settings. In a 16-month randomized controlled trial (follow-up period) conducted across three agroecological areas (dry mountain, plateau highland, and semi-arid) in Jabi Tehnan district, northwestern Ethiopia, treatment houses were equipped with HS combined with insecticide-treated nets (ITNs), while control houses received ITNs only. The intervention led to a significant 2.3-fold reduction in indoor malaria vector density, the primary entomologic outcome, largely influenced by An. gambiae s.l. mosquitoes. …

Characterizing Malaria Infections In Caribbean Lizards: Parasite Niche Expansion & Host Response, Sarah J. Pangburn

Dissertations, Theses, and Capstone Projects

Malaria is historically one of the most severe parasitic human diseases and is still responsible for over half a million deaths annually. Plasmodium species, the causative agents of malaria, are often characterized by two hallmark features of their asexual stages: the invasion of vertebrate red blood cells and the presence of hemozoin pigment as a byproduct of host hemoglobin digestion. Despite their evolutionary relatedness to mammalian Plasmodium, wildlife malaria parasites are understudied, leaving their vast genetic diversity to be explored. Lizard-infective malaria parasites, for example, include over 100 species of Plasmodium and present a diverse array of phenotypes, some …

Evaluation Of The Humoral Immune Responses To Plasmodium Vivax Circumsporozoite Protein (Csp)-Based Pre-Erythrocytic Vaccine Candidates, Jack Esquenazi

USF Tampa Graduate Theses and Dissertations

Malaria, caused by the apicomplexan Plasmodium spp. , is a major public health issue that impacts over one-third of the world’s population ,with Plasmodium vivax accounting for over 130 million clinical cases annually. The circumsporozoite protein (CSP) is the most abundant molecule on the surface of Plasmodium sporozoites and is considered a leading pre-erythrocytic stage vaccine candidate. CSP is essential for sporozoite maturation, migration, and invasion. Anti-CSP antibodies interrupt sporozoite migration and infection of hepatocytes thus reducing liver-stage burden. P. vivax CSP is composed of three subdomains: a highly polymorphic immunodominant central repeat region (CRR), conserved N-terminal ,and C-terminal subdomains. …

Partial Characterization Of Plasmodium Falciparum Genes Implicated In Altered Artemisinin Stress Response, Caroline F. Simmons

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic illness caused by the Plasmodium spp., with an estimated 247 million malaria cases reported in 2021 across 84 endemic countries. Treatment of the deadliest malaria parasite, P. falciparum, relies on artemisinin combination therapies (ACTs). However, while ACTs have greatly decreased malaria mortality, this progress is threatened due to artemisinin (ART) partial resistance and ACT failure in Southeast Asia and Sub-Saharan Africa. SNPs to the Kelch13 (K13) gene are a well-characterized marker for ART resistance. However, increasing evidence that resistance to ART mediated by genes not related to K13 SNPs prompts the need to characterize other novel …

Why Plasmodium Vivax And Plasmodium Falciparum Are So Different? A Tale Of Two Clades And Their Species Diversities, Ananias A. Escalante, Axl S. Cepeda, M. Andreína Pacheco

Harold W. Manter Laboratory of Parasitology: Library Materials

The global malaria burden sometimes obscures that the genus Plasmodium comprises diverse clades with lineages that independently gave origin to the extant human parasites. Indeed, the differences between the human malaria parasites were highlighted in the classical taxonomy by dividing them into two subgenera, the subgenus Plasmodium, which included all the human parasites but Plasmodium falciparum that was placed in its separate subgenus, Laverania. Here, the evolution of Plasmodium in primates will be discussed in terms of their species diversity and some of their distinct phenotypes, putative molecular adaptations, and host–parasite biocenosis. Thus, in addition to a current …

Complexity Of Malaria Transmission Dynamics In The Brazilian Atlantic Forest, Ana Maria Ribeiro De Castro Duarte, Licia Natal Fernandes, Fabiana Santos Silva, Igor Lucoves Sicchi, Luis Filipe Mucci, Izilda Curado, Aristides Ferrnandes, Antônio Ralph Medeiros-Sousa, Walter Ceretti-Junior, Mauro Toledo Marrelli, Eduardo Evangelista, Renildo Teixeira, Juliana Laurito Summa, Marcello Schiavo Nardi, Margoth Ramos Garnica, Ana Carolina Loss, Julyana Cerqueira Buery, Crispim Cerutti Jr., M. Andreína Pacheco, Ananias A. Escalante, Maria Anice Mureb Sallum, Gabriel Zorello Laporta

Harold W. Manter Laboratory of Parasitology: Library Materials

Plasmodium malariae and Plasmodium vivax are protozoan parasites that can cause malaria in humans. They are genetically indistinguishable from, respectively, Plasmodium brasilianum and Plasmodium simium, that is, parasites infecting New World non-human primates in South America. In the tropical rainforests of the Brazilian Atlantic coast, it has long been hypothesized that P. brasilianum and P. simium in platyrrhine primates originated from P. malariae and P. vivax in humans. A recent hypothesis proposed the inclusion of Plasmodium falciparum into the transmission dynamics between humans and non-human primates in the Brazilian Atlantic tropical rainforest. Herein, we assess the occurrence of human …

Parasite Of The Month. Hepatocystis, Imran Ejotre, Deeann Reeder, Kai Matuschewski, Juliane Schaer

Faculty Journal Articles

No abstract provided.

Malaria, Microbes, And Mice: The Role Of The Gut Microbiota On The Immune Response To Plasmodium Infection And The Treatment Potential Of Microbiota Modulation., Morgan L. Waide

Electronic Theses and Dissertations

Plasmodium infection leads to over 200 million cases of malaria and 400,000 deaths worldwide each year. These deaths are largely in children under the age of five and pregnant women [1]. Caused by transmission of Plasmodium parasites by the female Anopheles mosquito, malaria poses a risk for over 40 percent of the world’s population [1]. Despite worldwide efforts to eradicate malaria leading to a decrease in malaria-associated mortalities in the early 2000s [2], growing resistance to the available antimalarials and the lack of an effective, long-lasting vaccine has caused this decrease to plateau in recent years [1, 3-6]. Furthermore, malaria …

Plasmodium Impairs Antibacterial Innate Immunity To Systemic Infections In Part Through Hemozoin-Bound Bioactive Molecules., Christopher Lynn Harding

Electronic Theses and Dissertations

Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year which resulted in 405,000 deaths in 2018 [1]. One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through activities of heme oxygenase I (HO-I) )-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during …

Plasmodium Para-Aminobenzoate Synthesis And Salvage Resolve Avoidance Of Folate Competition And Adaptation To Host Diet, Joachim Michael Matz, Mutsumi Watanabe, Mofolusho Falade, Takayuki Tohge, Rainer Hoefgen, Kai Matuschewski

Pharmaceutical Sciences Faculty Publications

Folate metabolism is essential for DNA synthesis and a validated drug target in fast-growing cell populations, including tumors and malaria parasites. Genome data suggest that Plasmodium has retained its capacity to generate folates de novo. However, the metabolic plasticity of folate uptake and biosynthesis by the malaria parasite remains unresolved. Here, we demonstrate that Plasmodium uses an aminodeoxychorismate synthase and an aminodeoxychorismate lyase to promote the biogenesis of the central folate precursor para-aminobenzoate (pABA) in the cytoplasm. We show that the parasite depends on de novo folate synthesis only when dietary intake of pABA by …

The Polyphyly Of Plasmodium: Comprehensive Phylogenetic Analyses Of The Malaria Parasites (Order Haemosporida) Reveal Widespread Taxonomic Conflict, Spencer C. Galen, Janus Borner, Ellen S. Martinsen, Juliane Schaer, Christopher C. Austin, Christopher J. West, Susan L. Perkins

Harold W. Manter Laboratory of Parasitology: Library Materials

The evolutionary relationships among the apicomplexan blood pathogens known as the malaria parasites (order Haemosporida), some of which infect nearly 200 million humans each year, has remained a vexing phylogenetic problem due to limitations in taxon sampling, character sampling and the extreme nucleotide base composition biases that are characteristic of this clade. Previous phylogenetic work on the malaria parasites has often lacked sufficient representation of the broad taxonomic diversity within the Haemosporida or the multi-locus sequence data needed to resolve deep evolutionary relationships, rendering our understanding of haemosporidian lifehistory evolution and the origin of the human malaria parasites incomplete. Here …

Synthesis, In Vitro Characterization And Applications Of Novel 8-Aminoquinoline Fluorescent Probes, Adonis Mcqueen

USF Tampa Graduate Theses and Dissertations

Malaria is a parasitic disease that is caused by the plasmodium parasite. Plasmodium infection has affected man for thousands of years. With advances in drug discovery over the past century, malaria has evolved to possess resistance to most mainline therapeutics. This war of drug discovery vs plasmodium evolution continues to be fought to this very day, with attempts to eradicate malaria worldwide. Frontline treatments such as chloroquine, artemisinin, and atovaquone/proguanil have all seen parasitic resistance in strains of P. vivax as well as P. falciparum. While plasmodium possesses resistance to most classes of anti-malarials, the 8-aminoquinoline (8-AQ) class has …

Robust Odorant Recognition In Biological And Artificial Olfaction, Nalin Katta

McKelvey School of Engineering Graduate Student Theses & Dissertations

Accurate detection and identification of gases pose a number of challenges for chemical sensory systems. The stimulus space is enormous; volatile compounds vary in size, charge, functional groups, and isomerization among others. Furthermore, variability arises from intrinsic (poisoning of the sensors or degradation due to aging) and extrinsic (environmental: humidity, temperature, flow patterns) sources. Nonetheless, biological olfactory systems have been refined over time to overcome these challenges. The main objective of this work is to understand how the biological olfactory system deals with these challenges, and translate them to artificial olfaction to achieve comparable capabilities. In particular, this thesis focuses …

Analysis Of Antibody-Induced Plasmodium Falciparum Sporozoites Through Scanning Electron Microscopy, Sagorika Bera

USF Tampa Graduate Theses and Dissertations

Malaria is a devastating disease that continues to affect millions of people worldwide every year. Specifically, Plasmodium falciparum is the most common human malaria parasite, particularly in sub-Saharan Africa. P. falciparum causes the most malignant and debilitating symptoms with the highest mortality and complication rates. Even with the worldwide efforts of many researchers and organizations, the road to discovering a vaccine has been difficult and challenging. Due do to the improvements in in vitro liver stage assays as well as rodent models of mammalian malaria, pre-erythrocytic stages of malaria have become a more accessible target for experimental studies. These vaccine …

A Potent Antimalarial Benzoxaborole Targets A Plasmodium Falciparum Cleavage And Polyadenylation Specificity Factor Homologue., Ebere Sonoiki, Caroline L. Ng, Marcus C. S. Lee, Denghui Guo, Yong-Kang Zhang, Yasheen Zhou, M. R. K. Alley, Vida Ahyong, Laura M. Sanz, Maria Jose Lafuente-Monasterio, Chen Dong, Patrick G. Schupp, Jiri Gut, Jenny Legac, Roland A. Cooper, Francisco-Javier Gamo, Joseph Derisi, Yvonne R. Freund, David A. Fidock, Philip J. Rosenthal

Natural Sciences and Mathematics | Faculty Scholarship

Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC50 32 nM), Ugandan field isolates (mean ex vivo IC50 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED90 0.34 and 0.57 mg kg-1, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these …

Mitochondrial Heteroplasmy Contributes To The Dynamic Atovaquone Resistance Response In Plasmodium Falciparum, Sasha Victoria Siegel

USF Tampa Graduate Theses and Dissertations

Of the considerable challenges researchers face in the control and elimination of malaria, the development of antimalarial drug resistance in parasite populations remains a significant hurdle to progress worldwide. Atovaquone is used in combination with proguanil (Malarone) as an antimalarial treatment in uncomplicated malaria, but is rendered ineffective by the rapid development of atovaquone resistance during treatment. Previous studies have established that de novo mutant parasites confer resistance to atovaquone with a substitution in amino acid 268 in the cytochrome b gene encoded by the parasite mitochondrial genome, yet much is still unknown about how this resistance develops, and whether …

The Effects Of Phytohormones And Isoprenoids In Dihydroartemisinin-Induced Dormancy In The Erythrocytic Stages Of Plasmodium Falciparum, Marvin Duvalsaint Duvalsaint

USF Tampa Graduate Theses and Dissertations

Our ability to control malaria has been challenged by increasing antimalarial resistance. Plasmodium falciparum undergoes dormancy in the blood stages which is hypothesized to be a means by which they are able to survive under drug pressure. This helps select for resistant parasites which grow following removal of drug. The mechanisms behind dormancy and the subsequent recrudescence are not fully understood but translating knowledge from related organisms which undergo a similar phenomenon might shed some light. Higher plants utilize dormancy during the early development stages to survive under unfavorable conditions, increasing fitness of the seedling and ensuring viability when this …

Antimalarial Exoerythrocytic Stage Drug Discovery And Resistance Studies, Lynn Dong Blake

USF Tampa Graduate Theses and Dissertations

Malaria is a devastating global health issue that affects approximately 200 million people yearly and over half a million deaths are caused by this parasitic protozoan disease. Most commercially available drugs only target the blood stage form of the parasite, but the only way to ensure proper elimination is to treat the exoerythrocytic stages of the parasite development cycle. There is a demand for the discovery of new liver stage antimalarial compounds as there are only two current FDA approved drugs for the treatment of liver stage parasites, one of which fails to eliminate dormant forms and the other inducing …

Investigating The Effects Of Increasing Anti-Ama1, Anti-Msp1, And Anti-Msp2 In Preventing Malaria Incidence, April Skipper

Selected Honors Theses

Malaria is a life-threatening illness that 3.2 billion people, half of the world's population, are at risk of contracting. In 2015, there were 214 million malaria cases and 438,000 deaths caused by the disease. It is caused by Plasmodium parasites which infect humans through the bite of the Anopheles mosquito. The four species of Plasmodium that are known to cause malaria are P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. The symptoms of malaria greatly resemble symptoms of a common cold, so accurate diagnosis can be a challenge. Symptoms commonly include fever, headache, …

Identification And Characterization Of Interactors Of Plasmodium Falciparum Pfpk6, An Atypical Protein Kinase, Andi J. Cummins

Honors Undergraduate Theses

Plasmodium falciparum, the organism that causes the most prevalent and most virulent cases of malaria in humans, poses a major health burden on the developing world, especially in the tropical regions of Sub-Saharan Africa, Southeast Asia, and Latin America. The burden of the disease is intensified by the fact that the parasite has developed widespread resistance to all current antimalarial therapies, such as chloroquine. This drug resistance underscores the need to develop novel therapeutics that target the parasite, but show low toxicity in the human host. Protein kinases, because of their integral roles in cell signaling networks, are considered to …

A Forward Genetic Screen Identifies Factors Associated With Fever Pathogenesis In Plasmodium Falciparum, Phaedra J. Thomas

USF Tampa Graduate Theses and Dissertations

Infectious diseases that spread from person-to-person and continent-to-continent are a cause for concern for any health entity. One such disease is malaria, a mosquito-borne infection instigated by the protozoan parasite, Plasmodium falciparum. Hundreds of millions of people are affected annually and it is responsible for nearly 1 million deaths. It is the most fatal species causing malaria and proliferates in human red blood cells with a life cycle occurring every 48 hours. At this time, the parasite’s late stage form or schizont bursts from the erythrocyte releasing immune-inducing particles and infective forms (merozoites) into the bloodstream. The merozoites go …

Investigation Of Dual Stage Acridones As A Potent Malaria Treatment, Stephanie Huezo

Dissertations, Masters Theses, Capstones, and Culminating Projects

The need for potent antimalarials to prevent the emergence of drug resistant Plasmodium falciparum is urgent. Discovery of novel acridone chemotypes have shown promise for a new antimalarial drug treatment. Presently, two acridone chemotypes have intrinsic antimalarial potency against chloroquine sensitive and multidrug resistant parasites. Acridones lacking an N10 side chain are known as chemotype I acridones, whereas, chemotype II acridones are defined as having an alkyl side chain at the same position. The N10 substitution of chemotype II acridones is thought to target heme and inhibit hemozoin formation within the parasite’s digestive vacuole, and is known to provide synergistic …

A New Method For Estimating Species Age Supports The Coexistence Of Malaria Parasites And Their Mammalian Hosts, Joana C. Silva, Amy Egan, Cesar Arze, John L. Spouge, David G. Harris

Harold W. Manter Laboratory of Parasitology: Library Materials

Species in the genus Plasmodium cause malaria in humans and infect a variety of mammals and other vertebrates. Currently, estimated ages for several mammalian Plasmodium parasites differ by as much as one order of magnitude, an inaccuracy that frustrates reliable estimation of evolutionary rates of disease-related traits. We developed a novel statistical approach to dating the relative age of evolutionary lineages, based on Total Least Squares regression. We validated this lineage dating approach by applying it to the genus Drosophila. Using data from the Drosophila 12 Genomes project, our approach accurately reconstructs the age of well-established Drosophila clades, including …

Mmv Malaria Box Activity Screening In Dormant Plasmodium Falciparum Phenotypes, Sandra Galusic

USF Tampa Graduate Theses and Dissertations

The causative agent of malignant tertian malaria, Plasmodium falciparum undergoes an arrested growth phenotype of its erythrocytic stage when under drug-stress. Recent artemisinin treatment failures seem to be indicative of such induction followed by recrudescence rather than actual therapeutic failure. Likewise, P. vivax hypnozoites are the prototypic dormants and the latent infections for which they are responsible prove most difficult to treat. Dihydroartemisinin, an artemisinin-derivative, can be used to exploit this mechanism by inducing a dormant state in ring-stage P. falciparum parasites and in turn, their recovery may be used as a screening period for compounds that inhibit or foster …

Efficacy And Resistance Potential Of Jpc-3210 In Plasmodium Falciparum, Siobhan Marie Flaherty

USF Tampa Graduate Theses and Dissertations

Combating drug resistant malaria has been historically challenging, and remains so today. Recent reports from Southeast Asia show that Plasmodium falciparum is developing resistance to even our best defenses; artemisinin-based therapies. This development threatens to become a significant challenge in controlling malaria infections worldwide, making research into developing and characterizing new antimalarial drugs increasingly important. The purpose of this study was to characterize the resistance potential of novel antimalarial compound JPC-3210 in vitro using P. falciparum clones. JPC-3210 is a new long acting drug with potential to be used in combination with fast-acting drugs like artemisinins to cure drug resistant …

Altered Intraerythrocytic Development Phenotypes Of Artemisinin-Resistant Plasmodium Falciparum Confer A Fitness Advantage, Amanda Hott

USF Tampa Graduate Theses and Dissertations

Resistance to artemisinin combination therapies (ACTs) has emerged in southeast Asia threatening the most widely used treatment against antimalarial-resistant Plasmodium falciparum worldwide. Artemisinin resistance has been associated with a reduced rate of parasite clearance following treatment with an ACT and is attributed to increased survival of ring-stage parasites. Single nucleotide polymorphisms (SNPs) in kelch gene (K13) has been associated with delayed in vivo clearance half-life of artemisinin-resistant P. falciparum and is the only known molecular marker of resistance. The absence of reliable in vitro phenotypes for artemisinin resistance has limited our understanding of the resistance mechanism(s) and fitness costs, therefore …

Development Of Orally Bioavailable 4(1H)-Quinolones And 1,2,3,4-Tetrahydroacridin-9(10H)-Ones With Potent Anti-Malarial Activity, Jordany Richarlson Maignan

USF Tampa Graduate Theses and Dissertations

Although Malaria rates are on the decline due to the efforts of the World Health Organization and other organizations dedicated to the eradication of this disease, a relaxed attitude towards the development of new antimalarial entities would be flawed. Due to the emergence of resistance in the parasite, the almost 50% world-wide reduction in malarial death rates that have been produced over the past 15 years are threatening to be lost

New drugs are urgently needed and our approach focuses on the re-evaluation and optimization of the historic antimalarial ICI 56,780. Due to its causal prophylactic activity, along with its …

Environmental Data Analysis And Remote Sensing For Early Detection Of Dengue And Malaria, Md Zahidur Rahman, Leonid Roytman, Abdelhamid Kadik, Dilara A. Rosy

Publications and Research

Malaria and dengue fever are the two most common mosquito-transmitted diseases, leading to millions of serious illnesses and deaths each year. Because the mosquito vectors are sensitive to environmental conditions such as temperature, precipitation, and humidity, it is possible to map areas currently or imminently at high risk for disease outbreaks using satellite remote sensing. In this paper we propose the development of an operational geospatial system for malaria and dengue fever early warning; this can be done by bringing together geographic information system (GIS) tools, artificial neural networks (ANN) for efficient pattern recognition, the best available ground-based epidemiological and …