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Full-Text Articles in Parasitic Diseases

A Case Of Acute, Rapidly Fatal Disseminated Toxoplasmosis In A Pennsylvania Deer Hunter., Devi Parvathy Jyothi Ramachandran Nair, Nimesh Khanal, Muhammad Umer Riaz Gondal, Biraj Shrestha, Neil A. Hoffman, Anthony Donato Apr 2024

A Case Of Acute, Rapidly Fatal Disseminated Toxoplasmosis In A Pennsylvania Deer Hunter., Devi Parvathy Jyothi Ramachandran Nair, Nimesh Khanal, Muhammad Umer Riaz Gondal, Biraj Shrestha, Neil A. Hoffman, Anthony Donato

Tower Health Research Day

No abstract provided.


Targeting Cyp51 In The Treatment Of Acanthamoeba Keratitis, Ashkan Hassani, Vineet Sadarangani, Brad Haubrich Feb 2024

Targeting Cyp51 In The Treatment Of Acanthamoeba Keratitis, Ashkan Hassani, Vineet Sadarangani, Brad Haubrich

Annual Research Symposium

Acanthamoeba castellanii causes a rare but serious ocular infection called Acanthamoeba keratitis. Risk factors for infection include contact with contaminated water and poor hygiene of contact lenses. The first-line treatment is comprised of a months-long schedule of antibiotics. However, in cases where pharmacological interventions fail to address the infection, surgery may be necessary, with the continued risk of potential vision loss. Consequently, new treatments are needed, whether new pharmacological agents or new combination therapies with current agents. As an aerobic parasite, Acanthamoeba synthesizes ergosterol as a cell membrane insert, and ergosterol biosynthesis inhibitors (EBIs), common in antifungal pharmaceuticals, could potentially …


Microsporidiosis: Reviewing Clinical Presentation And Treatment Strategies, Julienne Zhou, Belinda Liu, Megan Dearmond, David Banach, Brad Haubrich Feb 2024

Microsporidiosis: Reviewing Clinical Presentation And Treatment Strategies, Julienne Zhou, Belinda Liu, Megan Dearmond, David Banach, Brad Haubrich

Annual Research Symposium

Microsporidiosis is an opportunistic infection caused by obligate intracellular pathogens within the taxon Microsporidia. Infection is zoonotic and has been associated with patients experiencing immunodeficiency, though incidence is increasing among other populations. Most commonly, the disease is gastrointestinal, typically by Enterocytozoon bieneusi and less commonly by Encephalitozoon intestinalis. Symptoms present with diarrhea and vomiting, and severe cases can lead to wasting and mortality. While the incorporation of anti-retroviral therapy for HIV patients has significantly decreased mortality in a subset of the vulnerable populations, treatment for microsporidiosis is still not standardized or well explored. Resistance to first-line treatment albendazole is increasing, …


Human-Bat Interactions In A Disease Emergence Hotspot: Implications For Human Health And Bat Conservation, Reilly Tempest Jackson Dec 2023

Human-Bat Interactions In A Disease Emergence Hotspot: Implications For Human Health And Bat Conservation, Reilly Tempest Jackson

Graduate Theses and Dissertations

Bats are an ecologically important taxon that can host zoonotic pathogens. Globally, many bat species are synanthropic and live closely with humans, often roosting in man-made structures. The spatial overlap between humans and bats creates opportunities for human-bat contact, which can lead to human exposure to bat-borne pathogens and conflicts that cause bat mortality. Despite this risk, little is known about the drivers and characteristics of these human-bat interactions in buildings and work is needed to understand this aspect of the wildlife-urban interface. In Chapter I, I present a literature review that identifies the geographic and taxonomic trends in reported …


Concepts In Animal Parasitology: Master Bibliography, Sue Ann Gardner Oct 2023

Concepts In Animal Parasitology: Master Bibliography, Sue Ann Gardner

Concepts in Animal Parasitology Textbook

Master bibliography for the open educational resource/open access textbook Concepts in Animal Parasitology, Scott L. Gardner and Sue Ann Gardner, editors, published by Zea Books, Lincoln, Nebraska, United States, 2024. This includes the references from literature cited and suggested supplemental reading.


From Myzocytosis To Cytostomal Nutrient Uptake And Transport By Intracellular Plasmodium Species, T. Y. Sam-Yellowe Aug 2023

From Myzocytosis To Cytostomal Nutrient Uptake And Transport By Intracellular Plasmodium Species, T. Y. Sam-Yellowe

Biological, Geological, and Environmental Faculty Publications

No abstract provided.


Black Bear Population Health Monitoring In The Southeast, Kathleen Elizabeth Riese Aug 2023

Black Bear Population Health Monitoring In The Southeast, Kathleen Elizabeth Riese

Masters Theses

Recent growth of the American black bear (Ursus americanus) population in the southeast raises concerns about the potential spread of density-dependent diseases among bears, particularly sarcoptic mange. However, research on the health of bears in this area is limited. We analyzed samples from 169 bears in the region. We performed Knotts tests, skin scrapes, fecal floats; Canine adenovirus (CAV), canine parvovirus (CPV), canine distemper virus (CDV), and Toxoplasma gondii serology, Trypanosoma, Rickettsia rickettsii, and apicomplexan PCR, and identified ecto- and endoparasites found grossly or histologically. We found that 69% (63 of 91) had microfilaria; genetic analysis identified …


Newer Surveillance Data Extends Our Understanding Of The Niche Of Rickettsia Montanensis (Rickettsiales: Rickettsiaceae) Infection Of The American Dog Tick (Acari: Ixodidae) In The United States, Catherine A. Lippi, Holly D. Gaff, Robyn M. Nadolny, Sadie J. Ryan Jun 2023

Newer Surveillance Data Extends Our Understanding Of The Niche Of Rickettsia Montanensis (Rickettsiales: Rickettsiaceae) Infection Of The American Dog Tick (Acari: Ixodidae) In The United States, Catherine A. Lippi, Holly D. Gaff, Robyn M. Nadolny, Sadie J. Ryan

Biological Sciences Faculty Publications

Background: Understanding the geographic distribution of Rickettsia montanensis infections in Dermacentor variabilis is important for tick-borne disease management in the United States, as both a tick-borne agent of interest and a potential confounder in surveillance of other rickettsial diseases. Two previous studies modeled niche suitability for D. variabilis with and without R. montanensis, from 2002-2012, indicating that the D. variabilis niche overestimates the infected niche. This study updates these, adding data since 2012.

Methods: Newer surveillance and testing data were used to update Species Distribution Models (SDMs) of D. variabilis, and R. montanensis infected D. variabilis, in …


Effect Of Temperature On The Microbiome Of A Laboratory Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna Mitchell May 2023

Effect Of Temperature On The Microbiome Of A Laboratory Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna Mitchell

Poster Presentations

Honors research poster.

Haemaphysalis longicornis is a species of tick native to eastern Asia, including eastern China, Japan, eastern Russia, and Korea. To date, it has invaded and has now established its existence in Australia, New Zealand, and several of the Pacific Islands. This species of tick has recently been introduced to the United States, having a confirmed sighting in November 2017 on a sheep farm in New Jersey and since establishing populations in 18 states along the east coast and Appalachia. Based on the existing locations of H. longicornis in its native regions, as well as in the United …


Effect Of Temperature On The Microbiome Of A Laboratory-Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna L. Mitchell May 2023

Effect Of Temperature On The Microbiome Of A Laboratory-Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna L. Mitchell

Undergraduate Honors Theses

Haemaphysalis longicornis ticks are invasive to the United States with potential to transmit several tick-borne pathogens that are native to the United States. Based on existing locations of H. longicornis in its native regions in Asia, as well as its invasive populations that are established in the United States, several geographic range prediction models have been produced to help understand future range expansion and distribution of this invasive tick in North America. Unfortunately, these models do not all agree and there is uncertainty associated with the potential geographic range expansion of H. longicornis ticks in North America. Climate can affect …


A Systematic Review Of Research On Treatment & Prevention Of The Neglected Tropical Disease Leishmaniasis, Aryn Akerberg May 2023

A Systematic Review Of Research On Treatment & Prevention Of The Neglected Tropical Disease Leishmaniasis, Aryn Akerberg

All Theses

Leishmaniasis is a life-threatening neglected tropical disease that is caused by the protozoa parasite, Leishmania. Over one million new human leishmaniasis cases occur each all over the world, affecting most the deeply impoverished regions of the world. The disease presents in three different forms: cutaneous leishmaniasis, mucocutaneous (mucosal) leishmaniasis, and visceral leishmaniasis. Symptoms can range from self-limiting lesion to more life-threatening conditions such as fever, kidney disease, and anemia. The Leishmania parasite is transmitted via the bite of the female phlebotomine sandfly and can infect many other mammals such as canines, rodents, bats, etc. The canine leishmaniasis epidemic is also …


Characterization Of Toxoplasma Gondii Calcium Regulator Proteins Tggt1_253640 And Tggt1_222060 For Toxoplasma Gondii Growth And Invasion, Abigail Delapenha Apr 2023

Characterization Of Toxoplasma Gondii Calcium Regulator Proteins Tggt1_253640 And Tggt1_222060 For Toxoplasma Gondii Growth And Invasion, Abigail Delapenha

Student Research Submissions

Toxoplasma gondii is an opportunistic apicomplexan parasite infecting humans and livestock. Infection in immunocompromised individuals can cause neurological damage and infection during pregnancy can lead to fetal death. These parasites engage in a complex life cycle, involving repeated invasion of the host cell and egress from the host cell. Calcium signaling is an important regulatory mechanism for many essential processes in the parasite, including gliding motility (actomyosin-dependent mode of motion), invasion, and egress. Our work here focuses on two previously uncharacterized calcium regulator proteins (TGGT1_253640 and TGGT1_222060). To characterize the role of these proteins in parasite viability and calcium regulation, …


A Systematic Review: Toxoplasma Gondii Infection And Drugs Of Abuse, Amani Sastry Feb 2023

A Systematic Review: Toxoplasma Gondii Infection And Drugs Of Abuse, Amani Sastry

Annual Research Symposium

No abstract provided.


First Bovine Vaccine To Prevent Human Schistosomiasis - A Cluster Randomised Phase 3 Clinical Trial, Allen G. Ross, Donald A. Harn, Delia Chy, Marianette Inobaya, Jerric R. Guevarra, Lisa Shollenberger, Yuesheng Li, Donald P. Mcmanus, Darren J. Gray, Gail M. Williams Jan 2023

First Bovine Vaccine To Prevent Human Schistosomiasis - A Cluster Randomised Phase 3 Clinical Trial, Allen G. Ross, Donald A. Harn, Delia Chy, Marianette Inobaya, Jerric R. Guevarra, Lisa Shollenberger, Yuesheng Li, Donald P. Mcmanus, Darren J. Gray, Gail M. Williams

Biological Sciences Faculty Publications

Objective

Schistosomiasis is a neglected tropical parasitic disease caused by blood flukes of the genus Schistosoma. Schistosoma japonicum is zoonotic in China, the Philippines, and Indonesia, with bovines acting as major reservoirs of human infection. The primary objective of the trial was to examine the impact of a combination of human mass chemotherapy, snail control through mollusciciding, and SjCTPI bovine vaccination on the rate of human infection.

Methods

A 5-year phase IIIa cluster randomized control trial was conducted among 18 schistosomiasis-endemic villages comprising 18,221 residents in Northern Samar, The Philippines.

Results

Overall, bovine vaccination resulted in a statistically significant decrease …


Multipatch Stochastic Epidemic Model For The Dynamics Of A Tick-Borne Disease, Milliward Maliyoni, Holly D. Gaff, Keshlan S. Govinder, Faraimunashe Chirove Jan 2023

Multipatch Stochastic Epidemic Model For The Dynamics Of A Tick-Borne Disease, Milliward Maliyoni, Holly D. Gaff, Keshlan S. Govinder, Faraimunashe Chirove

Biological Sciences Faculty Publications

Spatial heterogeneity and migration of hosts and ticks have an impact on the spread, extinction and persistence of tick-borne diseases. In this paper, we investigate the impact of between-patch migration of white-tailed deer and lone star ticks on the dynamics of a tick-borne disease with regard to disease extinction and persistence using a system of Itô stochastic differential equations model. It is shown that the disease-free equilibrium exists and is unique. The general formula for computing the basic reproduction number for all patches is derived. We show that for patches in isolation, the basic reproduction number is equal to the …


Estimating The Distribution Of Oryzomys Palustris, A Potential Key Host In Expanding Rickettsial Tick-Borne Disease Risk, Catherine A. Lippi, Samuel Canfield, Christina Espada, Holly D. Gaff, Sadie J. Ryan Jan 2023

Estimating The Distribution Of Oryzomys Palustris, A Potential Key Host In Expanding Rickettsial Tick-Borne Disease Risk, Catherine A. Lippi, Samuel Canfield, Christina Espada, Holly D. Gaff, Sadie J. Ryan

Biological Sciences Faculty Publications

Increasingly, geographic approaches to assessing the risk of tick-borne diseases are being used to inform public health decision-making and surveillance efforts. The distributions of key tick species of medical importance are often modeled as a function of environmental factors, using niche modeling approaches to capture habitat suitability. However, this is often disconnected from the potential distribution of key host species, which may play an important role in the actual transmission cycle and risk potential in expanding tick-borne disease risk. Using species distribution modeling, we explore the potential geographic range of Oryzomys palustris, the marsh rice rat, which has been …


A Short Introduction To Marine Parasitology: Marine Parasites Of Economic And Medical Importance, Klaus Rohde, Robin M. Overstreet Jan 2023

A Short Introduction To Marine Parasitology: Marine Parasites Of Economic And Medical Importance, Klaus Rohde, Robin M. Overstreet

Concepts in Animal Parasitology Textbook

Introduction

Parasitism, in this chapter, is defined as “a close association of two organisms, in which one—the parasite—depends on the other—the host—deriving some benefit from it. The benefit is often food” (Rohde, 2005b). Many bacteria, viruses, and fungi are parasitic but usually not studied by parasitologists sensu stricto; they are the domain of microbiologists. Parasites as defined here do not always harm their host; the border between so-called genuine parasites and other symbionts such as commensals is often blurred, and investigators who work on disease aspects tend to emphasis the pathogenic aspects and may not consider non-pathogenic species as truly …


Livestock Cattle As A Predictor Of Schistosomiasis Transmission In Nigeria, Oyetunde T. Oyeyemi, Oluyemi A. Okunlola, Zhiqiang Fu, Yang Hong, Jun-Hu Chen, Lisa M. Shollenberger Jan 2023

Livestock Cattle As A Predictor Of Schistosomiasis Transmission In Nigeria, Oyetunde T. Oyeyemi, Oluyemi A. Okunlola, Zhiqiang Fu, Yang Hong, Jun-Hu Chen, Lisa M. Shollenberger

Biological Sciences Faculty Publications

Livestock cattle have been widely linked to schistosomiasis epidemiology, but little is known about its contribution to schistosomiasis transmission in Nigeria. The aim of this study is to examine the association between prevalence of schistosomiasis and livestock cattle index in Nigeria. The study's data came from three sources: the demographic and health survey (DHS), the malaria indicators survey (MIS), and the expanded special project for the eradication of neglected tropical diseases (ESPEN). Analysis of variance, correlation, and logistic regression were used to evaluate the mean difference in schistosomiasis prevalence across geopolitical zones, the relationship between schistosomiasis prevalence and livestock cattle, …


Anthelmintic Resistance In Sheep Across Ireland And The Uk: A Literature Review Of The In Vivo Versus In Vitro Methods, Megan Tumulty Dec 2022

Anthelmintic Resistance In Sheep Across Ireland And The Uk: A Literature Review Of The In Vivo Versus In Vitro Methods, Megan Tumulty

SURE Journal: Science Undergraduate Research Experience Journal

Background: The animal welfare and production consequences of gastrointestinal nematode infections, namely Nematodirus battus, on sheep are compelling. The control of gastrointestinal infections has been heavily reliant on the administration of anthelmintics since their introduction into mainstream use in 1960. However, their frequent and often excessive use has resulted in anthelmintic resistance being reported extensively in several gastrointestinal nematode species. The prevalence of anthelmintic resistance as well as the increase in the number of cases of multiple-drug resistance in nematode populations now poses substantial hindrance on the viability of sheep production systems. However, despite the threat N. battus poses …


Species Data And Vector Modeling: Evaluating Datasets For Improved Models Of Ixodes Ricinus Tick Distribution In Europe Under A Changing Climate, Steven Jones Dec 2022

Species Data And Vector Modeling: Evaluating Datasets For Improved Models Of Ixodes Ricinus Tick Distribution In Europe Under A Changing Climate, Steven Jones

Electronic Theses and Dissertations

To increase capacity for monitoring and surveillance of tick-borne diseases, publicly available tick distribution and climate change datasets are required to create accurate predictive distribution models. It is difficult, however, to assess model accuracy and utility when using incomplete datasets.  The more recent development of comprehensive tick databases for Europe and availability of climate change scenarios from multiple IPCC Assessment Reports allows for improved modeling efforts. Multiple tick datasets were combined and three climate change projections were compared by predicting current and future distributions of Ixodes ricinus ticks in Europe using the MaxEnt species distribution model. Overall, much of Europe …


An Epidemiological Synthesis Of Emerging And Re-Emerging Zoonotic Disease Threats In Cameroon, 2000-2022 And Community Stakeholder Mapping, Nancy Tahmo Dec 2022

An Epidemiological Synthesis Of Emerging And Re-Emerging Zoonotic Disease Threats In Cameroon, 2000-2022 And Community Stakeholder Mapping, Nancy Tahmo

Capstone Experience

Introduction: Population factors such as urbanization, socio-economic, and environmental factors are driving forces for emerging/re-emerging diseases in Cameroon, and the effects of these are experienced differently across demographics. Indigenous rainforest communities in the Congo Basin, for example, suffer worse health outcomes compared to neighboring communities, like the Pygmies, who have a life expectancy of 22 years less than neighboring Bantus. It is important to characterize the risk of exposure of these vulnerable communities and map out, through a systematic review, descriptive epidemiological data around zoonoses, to inform preparedness and research efforts.

Methods: Following the PRISMA guidelines, a protocol was registered …


A Reactivation Of Ocular Toxoplasmosis During Pregnancy, Brett Garee Od, Ms, Sarah Dieter Od, Pete Liette Od Oct 2022

A Reactivation Of Ocular Toxoplasmosis During Pregnancy, Brett Garee Od, Ms, Sarah Dieter Od, Pete Liette Od

Optometric Clinical Practice

Background: Toxoplasma gondii is a parasite estimated to affect over 500 million people worldwide. The feline is the definitive host for the parasite and infection may be acquired or congenital via maternal transmission. Humans may acquire the infection by ingestion of raw or undercooked meats and vegetables, contaminated water, or exposure to infected cat feces. The infection is often benign, self-limiting, and asymptomatic for humans, but potentially life threatening to infants or the immunocompromised patient.

Case Report: A 22 year-old Caucasian female, pregnant at 12 weeks gestation, presented to the optometry service with acute symptoms of hazy vision …


Infection And Transmission Determinants Of Flea-Borne Rickettsioses, Hanna J. Laukaitis Aug 2022

Infection And Transmission Determinants Of Flea-Borne Rickettsioses, Hanna J. Laukaitis

<strong> Theses and Dissertations </strong>

The genus Rickettsia is comprised of Gram-negative, obligate intracellular bacteria that are spread by hematophagous arthropods. Elucidating the factors conferring rickettsial virulence has perplexed investigators for decades, complicated by the lack of efficient genetic tools necessary to uncover rickettsial- and vector-specific factors contributing to persistence. The advent of transposon mutagenesis has enabled the field to make vast developments in uncovering novel rickettsial mechanisms utilized in various host backgrounds. Thus, the aim of this study was to generate Rickettsia felis transposon mutants and characterize novel phenotypes associated with genetic disruption in an arthropod background. Distribution of rickettsiae is reliant on the …


Human Cryptosporidiosis: A Review And Staining Method, Amatullah Ahmad Aug 2022

Human Cryptosporidiosis: A Review And Staining Method, Amatullah Ahmad

Honors College

Cryptosporidiosis is increasingly emerging as the most significant cause of infectious diarrhea in humans and livestock. In humans, studies show that Cryptosporidiosis disease is more prevalent in the immunocompromised and young ones. However, outbreaks from contaminated water sources have caused disease in healthy adults, too. Two main species of the protozoan causative agent,Cryptosporidium parvum and Cryptosporidium hominis are responsible for most human infections. Cattle, pets, mice, and other livestock can transmit theCryptosporidiumparvumvariantsto humans through fecal transmission. Other species of Cryptosporidium can infect domestic animals, but their host range is narrow; therefore, they are not of significant concern to human health. …


Control Of Scabies In A Boarding School Using 5% Permethrin Applied On Lesion Only, Saleha Sungkar, Sri Wahdini, Aria Kekalih, Risa Rilanda, Hansen Angkasa, Sandra Widaty Jul 2022

Control Of Scabies In A Boarding School Using 5% Permethrin Applied On Lesion Only, Saleha Sungkar, Sri Wahdini, Aria Kekalih, Risa Rilanda, Hansen Angkasa, Sandra Widaty

ASEAN Journal of Community Engagement

Scabies is one of the most neglected tropical skin diseases in Indonesia. It is usually found in overcrowded communities with poor hygiene. The gold standard for scabies treatment is the whole-body topical application of 5% permethrin cream. However, the treatment causes inconvenience and stickiness for a prolonged period. The modification of topical treatment by applying only to the lesion yielded results similar with whole-body topical application. We consider using this mode of treatment to control the disease in a boarding school. The study was conducted from June to August 2019. All students were examined by dermatologists, and individuals who were …


Total Prevention: A History Of Schistosomiasis In Japan, Alexander Bay Jul 2022

Total Prevention: A History Of Schistosomiasis In Japan, Alexander Bay

History Faculty Articles and Research

In Japan, schistosomiasis was endemic in Yamanashi Prefecture and a few other hotspot areas where the Miya’iri snail lived. The parasite’s lifecycle relied on the intermediary Miya’iri snail as well as the human host. Parasite eggs passed into the agrarian environment through untreated night soil used as fertiliser or through the culture of open defecation in rural Japan. Manmade rice fields and irrigation ditches, night soil covered paddies and highly refined growing seasons put people in flooded rice paddies to intensively work the land in the spring and summer. The disease was equally dependent on human intervention in the natural …


Malaria: Existence Perpetuated By A Counterfeit Drug Industry, Nicholas Black Jun 2022

Malaria: Existence Perpetuated By A Counterfeit Drug Industry, Nicholas Black

Undergraduate Research Symposium

Malaria is a mosquito-borne disease that has plagued society for thousands of years. Malaria is often overlooked from the perspective of wealthier industrialized countries due to prevention efforts largely eliminating malaria from these locations. However, overlooking malaria’s continued global relevance is misinformed to the fact that nearly half the global population lives in regions at risk of malarial transmission. According to the CDC and WHO, such a high number of people at risk has subsequently led to an estimated 241 million cases and over 627 thousand deaths in 2020 alone. The purpose for the present research is to examine the …


Disrupting Monoallelic Expression Of Variant Surface Glycoprotein In Trypanosoma Brucei By A Non-Lethal Mutation In Class I Transcription Factor A, Sarah Platt May 2022

Disrupting Monoallelic Expression Of Variant Surface Glycoprotein In Trypanosoma Brucei By A Non-Lethal Mutation In Class I Transcription Factor A, Sarah Platt

Honors Scholar Theses

Human African trypanosomiasis (HAT) is a lethal disease caused by protozoan hemoflagellates of the genus Trypanosoma. Humans are vulnerable to two subspecies, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. At the crux of HAT lethality lie two uncommon genetic expression phenomena: monoallelic expression and antigenic variation. Combined, these mechanisms effectively shield trypanosomes from host immune systems, prolonging infections. Variant Surface Glycoproteins (VSGs) are the key outer membrane proteins involved in antigenic variation. By continuously changing the composition of cell surface antigens, trypanosomes can survive bouts of immunological detection and eventually traverse the blood-brain barrier. There are over two …


Transmission Risk Of Malaria Via Gas Flares In Africa, Elle Blake May 2022

Transmission Risk Of Malaria Via Gas Flares In Africa, Elle Blake

Health, Human Performance and Recreation Undergraduate Honors Theses

Gas flaring occurs at oil drilling sites around the world. It is a method to get rid of the extra gas, as well as to release pressure in emergency situations. The pollutants that are contributed to the air through routine gas flaring can be extremely harmful. Chemicals such as sulfur dioxide and methane are burned into the air we breathe (Baker Hughes, 2019). Not only does this have a direct impact on our health, but also on greenhouse gas emissions. The effects on greenhouse gas emissions impact diseases such as Malaria by increasing the temperature of our planet. The purpose …


Preclinical Characterization And Target Validation Of The Antimalarial Pantothenamide Mmv693183., Laura E. De Vries, Patrick A. M. Jansen, Catalina Barcelo, Justin Munro, Julie M. J. Verhoef, Charisse Flerida A. Pasaje, Kelly Rubiano, Josefine Striepen, Nada Abla, Luuk Berning, Judith M. Bolscher, Claudia Demarta-Gatsi, Rob W. M. Henderson, Tonnie Huijs, Karin M J Koolen, Patrick K. Tumwebaze, Tomas Yeo, Anna C. C. Aguiar, Iñigo Angulo-Barturen, Alisje Churchyard, Jake Baum, Benigno Crespo Fernández, Aline Fuchs, Francisco-Javier Gamo, Rafael V. C. Guido, María Belén Jiménez-Diaz, Dhelio B. Pereira, Rosemary Rochford, Camille Roesch, Laura M. Sanz, Graham Trevitt, Benoit Witkowski, Sergio Wittlin, Roland A. Cooper, Philip J. Rosenthal, Robert W. Sauerwein, Joost Schalkwijk, Pedro H. H. Hermkens, Roger V. Bonnert, Brice Campo, David A. Fidock, Manuel Llinás, Jacquin C. Niles, Taco W. A. Kooij, Koen J. Dechering Apr 2022

Preclinical Characterization And Target Validation Of The Antimalarial Pantothenamide Mmv693183., Laura E. De Vries, Patrick A. M. Jansen, Catalina Barcelo, Justin Munro, Julie M. J. Verhoef, Charisse Flerida A. Pasaje, Kelly Rubiano, Josefine Striepen, Nada Abla, Luuk Berning, Judith M. Bolscher, Claudia Demarta-Gatsi, Rob W. M. Henderson, Tonnie Huijs, Karin M J Koolen, Patrick K. Tumwebaze, Tomas Yeo, Anna C. C. Aguiar, Iñigo Angulo-Barturen, Alisje Churchyard, Jake Baum, Benigno Crespo Fernández, Aline Fuchs, Francisco-Javier Gamo, Rafael V. C. Guido, María Belén Jiménez-Diaz, Dhelio B. Pereira, Rosemary Rochford, Camille Roesch, Laura M. Sanz, Graham Trevitt, Benoit Witkowski, Sergio Wittlin, Roland A. Cooper, Philip J. Rosenthal, Robert W. Sauerwein, Joost Schalkwijk, Pedro H. H. Hermkens, Roger V. Bonnert, Brice Campo, David A. Fidock, Manuel Llinás, Jacquin C. Niles, Taco W. A. Kooij, Koen J. Dechering

Natural Sciences and Mathematics | Faculty Scholarship

Drug resistance and a dire lack of transmission-blocking antimalarials hamper 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 …