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Category: CTEGD Blog

Christopher West named 2023 Distinguished Research Professor

Christopher West

Christopher West, head of the Department of Biochemistry and Molecular Biology, a researcher in the Complex Carbohydrate Research Center and a member of CTEGD, belongs to a small group of internationally recognized parasite glycobiologists. His rigorous, transformative research explores cellular processes involving various structures, enzymes and roles of glycans, or sugar chains. His studies have identified fundamental cell-to-cell mechanisms of environmental sensing and signaling in glycobiology. Some of his seminal discoveries involve the biosynthesis and roles of novel glycan molecules in the model organism, Dictyostelium discoideum. One of his crucial contributions to glycobiology has been to describe at molecular resolution that organism’s biochemical response pathway to altered oxygen levels, allowing it to respond to its environment’s available oxygen. Since arriving at UGA, he has translated these findings to an opportunistic human pathogen, Toxoplasma gondii, which can grow and infect cells in low-oxygen environments. His research with collaborators at UGA and internationally has opened a new field of oxygen-sensing in protists, exploring how this environmental factor can control the behavior and virulence of pathogenic parasites.

All the pieces matter: UGA researchers collaborate to solve malaria puzzle

malaria parasites
Super-resolution microscopy showing malaria parasites infecting human red blood cells. credit: Muthugapatti Kandasamy, Biomedical Microscopy Core

They say what doesn’t kill you makes you stronger. Whoever coined that adage had probably never heard of Plasmodium.

It’s a microscopic parasite, invisible to the naked eye but common in tropical and subtropical regions throughout the world. Each year, millions of people are infected by Plasmodium and exposed to an even more debilitating—and often deadly—disease: malaria.

Malaria is one of the deadliest diseases known to man. It can lead to extreme illness, marked by fever, chills, headaches and fatigue. More than half the world’s population is at risk of contracting the disease, and those who develop relapsing infections suffer a host of associated costs.

Limited educational opportunities and wage loss lead to an often unbreakable cycle of poverty. Vulnerable populations are most at risk.

“When I’m teaching in an endemic area like Africa, it isn’t unusual to find a student who needs to sleep during part of the workshop because they have malaria,” researcher Jessica Kissinger said.

It’s a challenge she and her collaborators in the University of Georgia’s Center for Tropical and Emerging Global Diseases (CTEGD) are trying to combat.

When the Center was established in 1998, there were only a couple of faculty members studying Plasmodium. Now, 25 years later, it has become a world-class powerhouse of multidisciplinary malaria research. Scientists examine various species of the dangerous parasite, studying its life cycle and the mosquito that transmits it.

While Plasmodium seems to have superpowers that allow it to evade detection and resist treatment, CTEGD researchers are working together to innovate and transfer science from the lab to interventions on the ground.

A 50,000-piece puzzle with no edges

Plasmodium is a complex organism, and studying it is like putting together a jigsaw puzzle. Some researchers contribute pieces related to the blood or liver stages of the parasite’s lifecycle, while others provide insights about hosts interactions. One way UGA’s research connects with the global effort to eradicate malaria is PlasmoDb—a resource derived in part from Kissinger’s research that is now part of a host of databases under the umbrella of The Eukaryotic Pathogen, Vector and Host information Resource (VEuPathDB).

“Our group has been able to help many others when their research question crosses into an –omic,” Kissinger said, referring to in-house shorthand for domains like genomics, proteomics and metabolomics.

Kissinger, Distinguished Research Professor of genetics in the Franklin College of Arts & Sciences, became interested in malaria and Plasmodium during her postdoctoral training at the National Institutes of Health (NIH). Working from an evolutionary biology perspective, she’s interested in how the parasite has changed over time.

PlasmoDb, a database of Plasmodium informatics resources, is a tool developed in part by the work of Distinguished Research Professor Jessica Kissinger, who became interested in malaria during her postdoctoral training at the National Institutes of Health.

“I see it as an arms race,” Kissinger said. “I want to understand what moves they have and can make.”

To understand the parasite, you must dive deep into its genetic code.

Kissinger paired her work in Plasmodium genomics with her interest in computing by helping create the database with information from the Plasmodium genome project completed in 2002. The Malaria Host-Pathogen Interaction Center, one of her projects at UGA, was a seven-year, multi-institutional effort funded, in part, by NIH to create data sets that could be used in systems biology of the host-pathogen interaction during the development of disease.

“Wouldn’t it be neat if, from the beginning of infection all the way to cure, you knew everything that was going on in the organism all the time?” Kissinger said, noting the project’s goal.

They generated terabytes of data that, along with data from the global research community, are publicly accessible and reusable through PlasmoDB and other resources.

Being part of a group that is studying so many different aspects of malaria helps put Kissinger’s research into perspective. Now, in addition to understanding the parasite, she also thinks about tools needed to facilitate research from peers.

High-tech solutions rely on basic research

David Peterson, professor of infectious diseases in the College of Veterinary Medicine, noted that low-tech solutions have mitigated malaria’s human costs. He acknowledged, however, that their long-term goals required more.

“We have to acknowledge that low-tech solutions, such as mosquito nets, have saved lives,” Peterson said. “But to develop the high-tech solutions that will one day end malaria, we need basic research.”

Pregnant women are particularly vulnerable to malaria because their existing immunity to malaria fails to protect them during pregnancy. Placental malaria often results in  premature birth and low birth weight.

Peterson is interested in a binding protein that allows the parasite to adhere to the placenta. While many P. falciparum parasites have only one gene copy that encodes the placental binding protein,  Peterson is investigating Plasmodiumisolates with two or more slightly different copies.

But why isn’t one copy enough?

David Peterson
Professor David Peterson of the College of Veterinary Medicine acknowledges the importance of low-tech solutions like mosquito nets but said to mitigate its effects required better understanding at the genetic level.

That is the primary question Peterson is focused on. He wants to understand how Plasmodium uses extra copies to evade the immune system, distinguishing the role of each requires tools that Vasant Muralidharan, associate professor of cellular biology, has.

Muralidharan’s interest began when he contracted malaria himself. Through access to good health care, he made a full recovery, but the pain he endured remained. He wanted to understand this parasite. Even more, he wanted to make an impact with research.

His graduate training focused on biophysics, but soon his interest in Plasmodium resurfaced. He discovered there was a lack of tools to study the parasite on a genetic level.

“It’s like a house of cards, and each card is a gene,” Muralidharan said. “You can remove one and see what happens—does the house fall or remain standing?”

This is an illustration of the life cycle of the parasites of the genus, Plasmodium, that are causal agents of malaria.(Illustration by CDC/ Alexander J. da Silva, PhD; Melanie Moser)

In the days before CRISPR/Cas9, there wasn’t a precise way to remove genes. Muralidharan is among the pioneers of gene-editing techniques in Plasmodium.

Like Peterson, Muralidharan focuses on proteins secreted by the parasite. He studies the largely unknown process that allows the parasite to invade a red blood cell (RBC), replicate and escape. The lack of tools was a major hindrance, so Muralidharan created new ones.

These tools have been used by Muralidharan’s CTEGD and CDC colleagues to see how drugs might fail. Muralidharan’s laboratory can create mutant Plasmodium parasites that become resistant to a particular drug, and genome sequence databases allow researchers to check if that mutant is already circulating in malaria endemic regions.

Vasant Quote

Building a research bridge to endemic regions

Plasmodium vivax is the predominant malaria parasite in Southeast Asia. It causes “relapsing malaria” during which some parasites go “dormant” after entering the liver instead of reproducing. This phase is a major obstacle for current treatments.

CTEGD Director Dennis Kyle, GRA Eminent Scholar Chair in Antiparasitic Drug Discovery and head of the Department of Cellular Biology, became fascinated with the Plasmodium parasite early in his career, spending time living in Thailand and working in refugee camps where malaria is prevalent.

Dennis Kyle
CTEGD Director Dennis Kyle was moved to follow through with his work as a researcher on a trip to a refugee camp in Thailand. Upon seeing the challenges residents faced, he thought perhaps he should have become a physician. Instead, a local leader impressed upon him the impact you could have in generating new treatments that could benefit everyone. (Photo by Andrew Davis Tucker/UGA)

“When I first got to the refugee camp and saw the situation people were living in, I questioned my decision to become a scientist in the lab instead of becoming a physician,” Kyle said, recalling a camp he worked in that housed about 1,300 kids between the ages of 2 and 15. “There was a guy who was a leader in the group who probably had no more than an early high school education. He said, ‘Look at what you can do—you might generate something that would benefit all of us. The physicians we have in the camp can only work on a few people at a time.’”

Kyle’s laboratory is looking to repurpose medications that have antimalarial properties, a safe way to reduce the development time from lab to clinical use. He’s optimistic we will see a drug treatment that eliminates vivax malaria.

“That’s where UGA is playing a major role,” he said. “The Gates Foundation funded us to develop tools to study the dormant parasite in the liver. And we’ve been successful.”

One of Kyle’s collaborators is Samarchith Kurup, assistant professor of cellular biology, who studies the human immune response to Plasmodium infection.

“We use mouse models to delve into the fundamental host-parasite interactions, which you cannot do practicallyin humans,” Kurup said. “Our understanding of these fundamental processes gives rise to newer and better vaccination approaches and drugs.”

Another important CTEGD addition is Chet Joyner, assistant professor of infectious diseases, whose work has helped make it easier to study dormant parasites stateside.

Like other Plasmodium researchers, Joyner became interested in parasites at an early age. During an undergraduate parasitology class, he discovered how little was known about P. vivax. He was already interested in how diseases develop, so for graduate school he focused on the liver stage of vivax malaria. However, it was a difficult task.

Samarchith Kurup is an assistant professor of cellular biology studying the human immune response to Plasmodium infection. (photo credit: Lauren Corcino)
Samarchith Kurup is an assistant professor of cellular biology studying the human immune response to Plasmodium infection. (photo credit: Lauren Corcino)
Chet Joyner
Assistant Professor Chet Joyner discovered how little was known about Plasmodium vivax as an undergraduate student.

“At the time, the technologies weren’t there,” Joyner said. “Dennis was working on his system, but it wasn’t on the scene yet. I changed from studying the parasite to studying the animal model to understand pathogenesis and immunology in humans.”

Joyner joined UGA after completing his postdoctoral training at Emory University, where he developed a non-mouse animal model to study vivax malaria.

“We have to go to [Thailand] where people are infected and collect blood samples and then feed mosquitoes these samples to do the necessary studies,” Kyle said. “That’s been very impactful. We’ve gotten a lot of data out of it, and now with Chet’s model it all can be done under one roof.”

Joyner wants to understand the human immune response with a focus on vaccine development. Building on Muralidharan’s and other researchers’ findings of how the parasite interacts with the RBCs, Joyner’s vaccine program targets a specific protein in the parasite that inhibits the development of immunity.

“My colleagues have shown that if you knock this protein out in the parasite, the immune response in mice is actually great, and we are now working together to evaluate this in non-mouse models.” Joyner said.

Joyner also has collaborated with Belen Cassera, professor of biochemistry, to screen drug compounds. Cassera’s training focused on metabolism to find drug targets. She is particularly interested in how a drug functions.

“If we understand how the drug works, it will help us predict potential side effects in humans,” Cassera said. “We can’t predict everything, but knowing how it works gives you some confidence in whether it will work in humans.”

Cassera is focused on finding drugs that will treat the more lethal Plasmodium falciparum, the predominant species in Africa, which is rapidly becoming resistant to current treatments. Her work is complementary to Kyle’s.

“They run certain assays for the liver-stage infection, and our lab benefits because we want to know if the drug we are developing is specific for the blood stage or can tackle all stages,” Cassera said.

M. Belen Cassera
Professor Belen Cassera is identifying drugs that will treat the lethal Plasmodium falciparum, a predominant species of the parasite in Africa that has become resistant to many current treatments.

Don’t forget the mosquito

“Malaria is a vector-borne disease transmitted by a mosquito. You need to tackle not only the parasite in the human but also stop its transmission,” Cassera said. “CTEGD is unique because we can study the whole life cycle, including the mosquito.”

Michael Strand, H.M. Pulliam Chair of Entomology in the College of Agricultural and Environmental Sciences and a National Academy of Sciences Fellow, is an expert on parasite-host interactions. Instead of the human host, he is interested in mosquitoes. Recent work indicates blood feeding behavior of mosquitoes strongly affects malaria parasite development while the gut microbiota of mosquitos could lead to new ways to control populations. Having the SporoCore insectory on campus aids his research.

Michael Strand is an expert on parasite-host interactions. His research focuses on mosquitoes and their effects on malaria parasite development.
Michael Strand is an expert on parasite-host interactions. His research focuses on mosquitoes and their effects on malaria parasite development.

Established in 2020, SporoCore, under the management of Ash Pathak, assistant research scientist in the Department of Infectious Diseases, provides both uninfected and Plasmodium-infected Anopheles stephensi mosquitoes to researchers at UGA and other institutions. Like Joyner’s animal model, the insectory allows for research to be done in the U.S. that would otherwise require field work in an endemic country.

Old-school interventions like mosquito nets, combined with new drug therapies, have reduced the number of malaria deaths, which declined over the last 30 years before rising slightly during the COVID-19 pandemic. Great strides have been made to control and treat malaria—but not enough. New tools, like the ones being developed at CTEGD, are needed to keep pushing malaria’s morbidity and mortality rates in the right direction.

“The hard part—what can’t be done easily with the tools we already have—is being done,” Kyle said. “We just need new tools, which is one of the things that our center is really a leader in.”

 

This story was first published at https://research.uga.edu/news/all-the-pieces-matter-uga-researchers-collaborate-to-solve-malaria-puzzle/

Chet Joyner receives $1.1 million grant to study malaria vaccine

RESEARCH WILL BE IN COLLABORATION WITH YALE UNIVERSITY

Chet Joyner, PhD, a faculty member in the Center for Vaccines and Immunology and the Center for Tropical and Emerging Diseases in the College of Veterinary Medicine (CVM) at the University of Georgia, is the recipient of a $1.1 million grant from Open Philanthropy to perform preclinical testing of a vaccine designed to prevent reinfection from malaria.

“A vaccine that lessens the impact of this disease will have incalculable value in terms of lives saved and the quality of life of those in the affected areas,” said Lisa K. Nolan, DVM, PhD, dean of the CVM. “We are proud of Dr. Joyner’s work and that he has chosen to do it in the College of Veterinary Medicine at the University of Georgia.”

Joyner is collaborating with Dr. Richard Bucala, MD, PhD, of Yale University to test the vaccine that targets Plasmodium-encoded Macrophage Migration Inhibitory Factor (pMIF), a protein secreted by Plasmodium falciparum, a pathogen that causes malaria.

The science team for Open Philanthropy, which recommended grants to Joyner and Bucala for the three-year study, believes that vaccinating against pMIF may provide an important boost to the efficacy of existing malaria vaccines, according to a statement on its website, openphilanthropy.org.

Open Philanthropy is a Silicon Valley-based nonprofit which aims to use its resources to help others as much as possible. They fund work in many areas, including global health.

Joyner, who was recruited from Emory University to join the CVM in January of 2020, said the college is uniquely positioned to test the efficacy of the vaccine developed by Bucala at Yale.

“We are a strong malaria group with unique infrastructure and facilities that can support this necessary research within the CVM,” Joyner said.

Immunity to malaria is acquired naturally after exposure, but the disease can be fatal to children younger than five and debilitating up to age 10 because malaria parasites disrupt the immune system’s response with their own proteins that mimic the human Macrophage Migration Inhibitory Factor (MIF).

Not only does the resulting illness cause children to miss school, but it also leads to long-term cognitive decline due to nutritional deficiencies. Parents miss work to care for children and the economic impacts compound.

According to the World Health Organization’s 2022 World Malaria report, an estimated 247 million cases of malaria occurred worldwide in 2021 and 619,000 people died, mostly children under the age of five in sub-Saharan Africa.

This story was originally published at https://vet.uga.edu/cvm-researcher-wins-1-1-million-grant-to-study-malaria-vaccine/

The CTEGD Cytometry Shared Resource Lab is growing!

CTEGD’s Cytometry Shared Resource Laboratory recently added a Malvern Panalytical NanoSight NS300 to their suite of cytometry instruments. This was a donation from the laboratory of Dr. Stephen Hajduk.

The NanoSight allows rapid analysis of the size distribution and concentration of all types of nanoparticles from 0.01 – 1 µm in diameter.  It is important to monitor and control the isolation and purification of extracellular vesicles (EVs) while conducting research into their function. NanoSight NTA (Nanoparticle Tracking Analysis (NTA) utilizes the properties of both light scattering and Brownian motion to provide quick and easy characterization of both the size and concentration of vesicles in aqueous buffers, giving confidence in the quality of the sample used in any downstream experiments.

Researchers across the UGA campus are investigating the role of EVs in T. brucei and N. fowleri infections, neural stem cell extracellular vesicle uptake and neutrophil uptake of exosomes isolated from cystic fibrosis sputum.

The NanoSight is the second instrument CSRL added in 2022 (see the Cytek Aurora Spectral Cytometer announcement) and increases the number of cytometry instruments available for CTEGD and the UGA research community use to 11.

The CSRL continues to provide access to state-of-the-art cytometry analyzers and sorters to researchers at the University of Georgia and across the scientific community. In addition to the instruments, the facility also provides expert advice and consultation for the design and analysis of flow experiments.

Jessica Kissinger is special guest on podcast

Jessica Kissinger was recently the guest researcher on the podcast Talking Biotech with Dr. Kevin Folta.

Show notes:

Parasites are known contributors to human disease and suffering, spanning a wide range of organisms. Dr. Jessie Kissinger from the University of Georgia has spent the last two decades curating genomic data from hundreds of parasites, their vectors and hosts. The information helps researchers generate hypotheses about parasites, and presents fertile resources for comparing genomes and understanding similarities and differences across this diverse set of organisms.

Listen to the podcast: https://share.transistor.fm/s/768d4a83

New Confocal Microscope at the Biomedical Microscopy Core

The University of Georgia’s Biomedical Microscopy Core has recently acquired a Zeiss LSM 980 confocal microscope with Airyscan2 and Multiplex Mode for confocal and super-resolution imaging.

This new state-of-art microscope is capable of fast, gentle, and simultaneous imaging of live and fixed samples with up to 5 colors (Blue, green, Red, Far-Red & NIR), and resolving structures up to 120 nm. It can be used for a wide array of imaging applications including protein co-localization, cytoskeletal studies, tiling of large tissue samples or a lot of cells, spectral imaging and unmixing of diverse fluorophores, and Z-stack 3D/4D imaging. It has an inverted microscope stand and environmental chamber with temperature control and CO2 for long-term live imaging. Moreover, the LSM 980 is fitted with seven different laser lines (405, 458, 488, 514, 543, 633, and 730 nm) and 32 channel GaAsP PMT + 2 channels MA-PMT detectors for performing spectral detection of a wealth of fluorescent labels from 380 nm to NIR range. The presence of Airyscan2 and Multiplex Mode allows fast imaging of samples at super-resolution levels.

The new instrument was purchased with funding from the UGA Office of Research and BMC (lease). It has been installed already at the Core and is available for training and use. Please contact Dr. M. Kandasamy, the Director of BMC for training, and refer to the Core website for further details about the instrument and fees.

The Biomedical Microscopy Core is open to all UGA researchers as well as researchers outside of UGA.

UGA researcher uncovers humans’ natural weapon against malaria

UGA’s Samarchith “Sam” Kurup, assistant professor of cellular biology, has been awarded a five-year National Institutes of Health grant to study the natural immune response to the Plasmodium parasite—which causes malaria—in liver cells. (photo credit: Lauren Corcino)

Samarchith “Sam” Kurup grew up in India, and he’s always been aware of the impact of malaria.

In 2020 there were an estimated 241 million cases of malaria worldwide and an estimated 627,000 deaths, according to a recently released World Health Organization Fact Sheet. Eighty percent of the malaria-related deaths in Africa are children under the age of 5. The relapsing nature of the disease leads to educational and employment loss that has long-term economic impacts for both the individual as well as society.

“Malaria is huge global problem,” said Kurup, a member of UGA’s Center for Tropical and Emerging Global Diseases. “Almost half of the world’s population is currently at risk of contracting malaria.”

Kurup began his training in veterinary medicine in India, where he became hooked on parasitology, then continued his studies at UGA. While pursuing his Ph.D. he worked in Rick Tarleton’s lab, studying a parasitic disease that affects both animals and humans—his first introduction to human immunology. He continued his training in immunology as a postdoctoral researcher in John Harty’s lab at the University of Iowa.

Combining parasitology with immunology prepared him to tackle malaria.

Malaria is one of the most studied parasitic diseases, yet the Plasmodium parasite that causes it keeps evading attempts to treat the infection in humans. This is largely due to its complex life cycle and the ability of the parasite to evolve drug resistance. In addition to life stages that occur in the mosquito, which transmits the Plasmodium parasite to humans, there are two life stages in humans—a short phase of initial development in the liver, followed by an infection of the blood cells that causes clinical disease.

“A lot of research has been focused on the blood stage in humans, as this is when a person is symptomatic,” said Kurup, assistant professor of cellular biology in the Franklin College of Arts and Sciences. “But we now recognize that if we want to stop malaria, we need to stop it in its tracks in the liver before accessing the blood, and for that we need to understand the liver stage.”

Kurup, a member of UGA’s Center for Tropical and Emerging Global Diseases, trained in parasitology and immunology. He hopes that uncovering how the human immune system naturally fights malaria in the liver stage will lead to an effective malaria vaccine. (photo credit: Lauren Corcino)

Kurup has been awarded a five-year National Institutes of Health grant to study the natural immune response to the Plasmodium parasite in liver cells.

“The liver stage is short and can be difficult to study in the laboratory,” he said. “There are also practical and ethical limitations to studying the liver stage of malaria in humans. We are hoping to tease apart the basic principles of immune responses during this stage using the mouse model.”

Kurup’s preliminary studies have shown that a group of signaling proteins called type 1 interferons play a role in the destruction of Plasmodium parasites in the liver. His newly funded project will fill a gap in the malaria knowledge base by using a combination of in vitro study and in vivo experiments to determine the molecular processes that eliminate Plasmodium parasites in liver cells. His group recently developed a transgenic parasite line that can be used to genetically alter its host cell.

“This strain is a game changer for our line of research because we can now determine how our liver cells would naturally eliminate the parasite, and maybe why it sometimes fails,” he said.

In a study recently published in Cell Reports, Kurup and colleagues used the genetically altered parasite to inhibit signaling by type 1 interferons and showed that this protein has a direct role in the control of malaria. Their study also revealed that other natural immune mechanisms may be active in controlling malaria in liver cells. The project funded by the new grant will delve further into these mechanisms.

“In addition to taking us a step closer to the control and possible eradication of malaria, this project will expand our knowledge so that we can better reduce the burdens of this illness in our society,” he said.

Kurup is hopeful that uncovering how the human immune system naturally fights malaria in the liver stage will lead to an effective malaria vaccine.

“I really believe that bringing together our knowledge in parasitology and approaches in immunology is key to uncovering new information on this elusive life stage in malaria,” he said. “There is no better place to do this, considering the intellectual and material resources we have at our disposal at UGA and the CTEGD.”

 

This story was first published at https://research.uga.edu/news/uga-researcher-uncovers-humans-natural-weapon-against-malaria/

Researchers discover potential treatment for Chagas disease

The skeletal muscle of a mouse infected with Trypanosoma cruzi is shown under a microscope. (Submitted by Fernando Sanchez)
The condition affects tens of millions across the Americas but lacks effective treatments

Researchers from the University of Georgia have discovered a potential treatment for Chagas disease, marking the first medication with promise to successfully and safely target the parasitic infection in more than 50 years.

Human clinical trials of the drug, an antiparasitic compound known as AN15368, will hopefully begin in the next few years.

Distinguished Research Professor Dr. Rick Tarleton of the Center for Tropical and Emerging Global Diseases at the Paul D. Coverdell Center for Biomedical and Health Sciences on Thursday, May 8, 2008. Dr. Tarleton is researching the effects of drug treatments on Chagas’ disease.

“I’m very optimistic,” said Rick Tarleton, corresponding author of the study and a UGA Athletic Association Distinguished Professor in the Franklin College of Arts and Sciences and member of the Center for Tropical and Emerging Global Diseases. “I think it has a really strong chance of being a real solution, not just a stand-in for something that works better than the drugs we currently have.”

The new drug works by targeting the parasite that causes the disease, Trypanosoma cruzi, also known as T. cruzi.

Nearly all people infected with the parasite experience flu-like symptoms such as fever, headaches and vomiting. However, after their immune response kicks in, their symptoms may subside.

But for 30% to 40% of patients, the infection can result in severe heart damage that can be both debilitating and life-threatening.

New drug is 100% effective in eliminating T. cruzi

Published in Nature Microbiology, the study found the new medication was 100% effective in curing mice, as well as non-human primates that were naturally infected by the parasite at a research facility in Texas. The animals also experienced no significant side effects from exposure to the drug.

Over the past several decades, previous treatment candidates went straight from experimental infections in mice to human clinical trials, where they failed to cure the infection. The new drug’s efficacy in non-human primates bodes well for how it will perform in humans.

“We’ve got something that is as close to effective as it can be in what is as close to a human as it could be, and there aren’t any side effects. That really de-risks it by a lot going into humans,” Tarleton said. “It doesn’t make it fail-safe, but it moves it much further along.”

Current medications to treat T. cruzi infection not ideal

T. cruzi is carried by blood-sucking insects known as kissing bugs. The insects can be found throughout North, Central and South America.

In addition to a nasty bite, the creatures carry the T. cruzi parasite, which is transmitted through their fecal matter. Victims can become infected when they unknowingly rub the insect’s feces into their eyes, nose or an open wound.

The infection may also be transmitted through organ transplants, from a pregnant person to their fetus or through contaminated food. However, infections from these pathways are less common.

The go-to medications used to treat Chagas aren’t terrible, Tarleton said, but they’re not ideal. They can pack some serious side effects and they’re not reliably effective, but they’re currently the only treatment option.

Patients also have to take the drugs for two months. And even the common but mild side effects like headache or nausea get old after a few weeks. As a result, about one in five people being treated for the disease stop taking their medications before they have a chance to cure the infection.

“Plus they have variable efficacy, and it’s not predictable,” Tarleton said. “I think most physicians in Latin America have to say, ‘We have a drug. It’s going to make you feel bad, and two months later after we finish it, we’re not really going to be able to tell you if it worked or not.’

“It’s really not a good inducement to take the medication.”

Chagas disease common in Latin American countries

Tens of millions of people across the Americas are infected with the parasite that causes Chagas disease. But it doesn’t get much media attention.

It’s most common in Latin American countries, particularly in low-income areas where housing isn’t ideal. Some of the countries with the highest rates of the disease include Bolivia, Venezuela, Argentina, Chile, Mexico and Brazil.

In homes with thatched roofs, mud walls or inadequate protection from the elements, kissing bugs thrive, making infection more likely.

Chagas disease poses significant risk to pets

The Centers for Disease Control and Prevention estimates around 300,000 people infected with the parasite currently live in the U.S. But because the condition isn’t a huge threat in places with good housing options, Chagas disease treatment and prevention doesn’t get much research funding.

There is growing concern about the T. cruzi infection rate among outdoor pets in the U.S., however. Working dogs and other pets that spend extended periods of time outside are contracting the parasite at an alarming rate.

“There are areas where the infection rates are 20% to 30% new infections per year,” Tarleton said. “Those tend to be severe infections where the dogs either die or develop a disease that makes them unable to work.”

Tarleton hopes to partner with veterinary pharmaceutical companies in the future to create a drug to treat the infection in pets as a means of funding diagnostics and medication purchases in Latin America.

For the present study, Tarleton partnered with colleagues at Anacor Pharmaceuticals, Texas A&M University, the University of Texas, the University of Kansas and Pfizer. Angel Padilla, Wei Wang, Dylan Orr, Brooke White, Arlene George and Huifeng Shen from UGA’s Center for Tropical and Emerging Global Diseases and the Department of Cellular Biology are co-authors on the paper.

 

Story by Leigh Beeson. It was first published at https://news.uga.edu/researchers-discover-potential-treatment-for-chagas-disease/

In the News: New study from the Tarleton Research Group

Rick Tarleton and colleagues recently published their new study, “Discovery of an orally active benzoxaborole prodrug effective in the treatment of Chagas disease in non-human primates” in Nature Microbiology. Check out these news stories about the study.

Behind the paper: New Hope for Treatment of a Very Neglected, Neglected Tropical Disease (Nature Microbiology)

Possible new treatment identified for neglected tropical disease (Science.org)

Researchers discover potential treatment for Chagas disease (Mirage News)

Researchers discover potential treatment for Chagas disease (Science Daily)

Researchers discover potential treatment for Chagas disease (Medical Xpress)

Chagas disease potential treatment: ‘I think it has a really strong chance of being a real solution’ (Outbreak News Today)

Promising New Drug May Effectively Treat Chagas Disease (Technology Networks)

Researchers discover potential treatment for Chagas disease (Newswise)

Potential Treatment for Chagas Disease (Labroots)

New Compound Shows Promise for Treating Chagas Disease (GEN)

Could Researchers Have Discovered a Chagas Disease Treatment? (PatientWorthy)

In the News: Christopher Rice quoted in news stories on Naegleria fowleri

Assistant Research Scientist Christopher Rice is quoted in news stories about the brain-eating amoeba Naegleria fowleri

Swimming in freshwater? Here’s what to know about the rare brain-eating Naegleria fowleri. (USA Today)

Iowa lake beach temporarily closed after swimmer contracts rare brain-eating amoeba infection (Daily News)

Missouri swimmer infected with rare brain-eating amoeba, likely from lake in Iowa (CBS News)

Swimmer at Lake of Three Fires State Park infected with brain-eating amoeba (The Gazette)

Man Infected With a Brain-Eating Amoeba While Swimming in Iowa Lake (Now This News)