University of South Florida researchers continue to hone the high-volume screening of compounds that may lead to optimal drugs to combat the rare but deadly infection caused by the brain-eating amoeba Naegleria fowleri.

Distinguished USF Health Professor Dennis Kyle, PhD, who has studied the parasite since the early 1980s, was a featured speaker Sept. 9 at the Second Annual Amoeba Summit in Orlando, FL. The summit brings together health care professionals to spread awareness about risk, diagnosis and the need for research to find effective treatments against primary amebic meningoencephalitis (PAM). The infection is caused by Naegleria fowleri, which flourishes in warm freshwater lakes. Florida, Texas and California are states with the most reported cases of PAM.

Distinguished USF Health Professor Dennis Kyle, PhD, is among a select group of researchers across the country focusing on drug discovery for the rare but deadly infection caused by Naegleria fowleri, commonly known as the brain-eating amoeba. – Photo by Christopher Rice

Dr. Kyle, a member of the USF College of Public Health Global Infectious Diseases Research group, leads a National Institutes of Health-funded study to find faster-acting drugs that might be combined with existing therapies to significantly increase survival rates of patients who contract infections from these pathogenic free-living amoebae. He is among a select group of researchers across the country who focus on this neglected infectious disease.

PAM usually affects healthy children and young adults who engaged in swimming, diving or other water activities that may cause contaminated water to enter the nose.  Once the parasite crosses into the sinuses, the amoeba invades the frontal brain where the infection destroys brain tissue. It kills more than 97 percent of its victims within days. An Orlando teen recently became only the fourth person known to survive an infection by Naegleria fowleri.

The amoeba moves so quickly that by the time doctors definitively identify Naegleria fowleri as the cause of meningitis, it is often too late for existing treatments to work.

“With such a high fatality rate, the odds are likely stacked against any patient who comes into the hospital with this organism,” Dr. Kyle said. “It is very important to develop rapid laboratory diagnostics and drugs that kill the amoeba quicker, so that we have more survivors.”

At the summit, Dr. Kyle highlighted the following approaches that USF is taking to discover a new drug. His laboratory collaborates on different drug discovery projects with Georgia State, USF Chemistry and the Center for Drug Discovery and Innovation, and the biotechnology company Mycosynthetix.

• Working to turn compounds that demonstrate the most promising chemical activity against the brain-eating amoeba into drugs.
• Screening libraries of small molecules and natural products to identify new “hits.” Fungi metabolites have become a promising new source.
• Repurposing drugs that may work against the amoeba — either those approved to treat a different disease or drugs tested in clinical trials but not approved.

USF Health/VA infectious diseases physician Sandra Gompf, MD, with Dr. Kyle at this year’s Amoeba Summit. After Dr. Gompf lost her 10-year-old son to amoebic meningoencephalitis, she and her husband, also a doctor, launched an Amoeba Season awareness campaign to help educate the public on ways to prevent the parasitic infection. – Photo by Christopher Rice

As they aim to shorten the timeline from discovery of a new drug to treating patients, researchers are also seeking to better understand how the brain-eating pathogen works.

Studies with mice have shown that a microscopic droplet of water containing 1,000 of the pathogenic organisms can cause the same infection as that seen in humans, Dr. Kyle said. But, researchers still don’t know why some people get sick when exposed to the amoeba and others do not.

“Is it the numbers of amoeba, or something about the person’s immune system? Nothing really ties a string between getting infected and not getting infected,” Dr. Kyle said in an interview last month with ABC News Nightline.

For the full ABC News story including comments from Dr. Kyle, click here.

For more on the Amoeba Season campaign, visit www.amoeba-season.com.

Tampa, FL (Nov. 10, 2015) — A University of South Florida (USF) Center for Global Health & Infectious Diseases Research team has demonstrated a new screening model to classify antimalarial drugs and to identify drug targets for the most lethal strain of malaria, Plasmodium falciparum.

The National Institutes of Health-funded study appeared online Nov. 6 in the journal Scientific Reports.

Half the world’s population is at risk for malaria, a mosquito-borne disease becoming increasingly resistant to the drug artemisinin.

The malaria parasite is becoming increasingly resistant to the drug artemisinin as the front-line treatment to combat the mosquito-borne disease, even though artemisinin is given as a combination therapy with another antimalarial drug.

The USF research provides a better understanding how antimalarial drugs work, thus adding ammunition in the race to overcome the spread of multidrug-resistant malaria – a public health threat that could  potentially undermine the success of global malaria control efforts.

The global health researchers used a collection of malaria parasite mutants that each had altered metabolism linked to defect in a single P. falciparum gene. They then screened 53 drugs and compounds against 71 of these P. falciparum piggyBac single insertion mutant parasites. Computational analysis of the response patterns linked the different antimalarial drug candidates and metabolic inhibitors to the specific gene defect.

This novel chemogenomic profiling revealed new insights into the drugs’ mechanisms of action and most importantly identified six new genes critically involved P. falciparum’s response to artemisinin, but with increased susceptibility to the drugs tested.

“That represents six new targets potentially as effective as artemisinin for killing the malaria parasite,” said the study’s co-senior author Dennis Kyle, PhD, a Distinguished USF Health Professor in the Department of Global Health, USF College of Public Health.  “There is definitely a sense of urgency for discovering new antimalarial drugs that may replace artemisinin, or work better with artemisinin, to prevent or delay drug resistance.”

From left, Dr. John Adams, Dr. Rays Jiang and Dr. Dennis Kyle are members of USF’s Center for Global Health & Infectious Diseases Research team.

The multi-faceted team of USF scientists worked with researchers from the University of Notre Dame’s Eck Institute for Global Health to undertake the chemogenomic profiling of P. falciparum for the first time.

“The methodology used in the study highlights the importance of team-based interdisciplinary research for cutting-edge scientific innovation by combining the tools of drug discovery methods with functional genomics and computational biology analysis. We are very happy to have such an important result published in the first year of a five-year NIH grant,” said co-senior author John Adams, PhD, Distinguished University Health Professor in the Department of Global Health, USF College of Public Health. “Equally important are the enormous efforts by the cadre of talented postdoctoral researchers and graduate students who were critical for making this type of challenging scientific study a success.”

“That interdisciplinary collaboration is where the power of this work comes to light,” Dr. Kyle said. “It helps us develop the tools, the molecular techniques we need to rapidly mine huge amounts of data and to discover new drug targets in ways not previously feasible.”

P. falciparum causes three-quarters of all malaria cases in Africa, and 95 percent of malaria deaths worldwide. It is transmitted to humans by the bite of an infected mosquito, which injects the one-celled malaria parasites from its salivary glands into the person’s bloodstream.

Half the world’s population is at risk of contracting malaria, so any decrease in artemisinin’s effectiveness could result in more deaths.

The USF study was supported by grants from the NIH, National Institute of Allergy and Infectious Diseases (NAID).

Microscopic image of malaria parasite P. falciparum

Article citation:
Anupam Pradhan, Geoffrey H. Siwo, Naresh Singh, Brian Martens, Bharath Balu, Katrina Button-Simons, Asako Tan, Min Zhang, Kenneth O. Udenze, Rays H.Y. Jiang, Michael T. Ferdig, John H. Adams & Dennis E. Kyle. “Chemogenomic profiling of plasmodium falciparum as a tool to aid antimalarial drug discovery.” Scientific Reports, 5, Article number 15930 (2015). doi: 10.1038/srep15930.

About USF Health
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, and the USF Physician’s Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation.  For more information, visit www.health.usf.edu

Media contact:
Anne DeLotto Baier, USF Health Communications
(813) 974-3303 or abaier@health.usf.edu

Among the microbes targeted is the brain-eating amoeba Naegleria fowleri

Tampa, FL (Sept. 3, 2015) — University of South Florida College of Public Health researchers were recently awarded a National Institutes of Health (NIH) grant to identify optimal drug candidates that could ultimately lead to a fast-acting treatment for rare but deadly infections caused by microscopic free-living amoeba (FLA) commonly found in warm freshwater lakes and rivers and in soil. The $425,000 award from the NIH’s National Institute of Allergy and Infectious Diseases is for the first two years of a five-year funding period, which could total $1.7 million over five years.

“Our ultimate goal for this project is to develop at least one new fast-acting drug that could be combined with existing therapies to significantly increase survival rates of patients who contract FLA infections of the central nervous system,” said principal investigator Dennis Kyle, PhD, a distinguished USF Health professor in the Department of Global Health, USF College of Public Health.

Dennis Kyle, PhD, distinguished USF Health professor, with research team members Christopher Rice, PhD, and Beatrice Colon, PhD candidate.

Dr. Kyle’s team will work with David Boykin, PhD, professor of chemistry at Georgia State University, who makes the antimicrobial compounds that USF is developing.

The new grant will build upon previous NIH-funded work by the USF researchers, who have already zeroed in on two new chemical compounds 500 times more potent than existing drugs used to combat the almost always fatal infection caused by the brain-eating amoeba known as Naegleria fowleri.  The new study will expand the screening and development of the most promising drug candidates to target Acanthamoeba spp, as well as Naegleria fowleri.

Naegleria fowleri causes primary amoebic meningoencephalitis (PAM), a rare disease that kills more than 97 percent of its victims within days. PAM is usually contracted by healthy children and young adults who engaged in swimming, diving or other water activities that may forcefully push contaminated water up the nose.  Once in the nose, the amoeba moves quickly to the brain where the infection destroys brain tissue.

PAM cases tracked by the Centers for Disease Control and Prevention have been most prevalent in Florida, California and Texas, and some officials believe that rising temperatures could increase the number and geographic range of the heat-seeking amoeba  and potentially lead to more cases.

Microscopic image of the brain-eating amoeba Naegleria fowleri.

More pervasive than Naegleria fowleri, multiple species of Acanthamoeba cause granulomatous  amoebic encephalitis (GAE), a life-threatening infection of the nervous system most often affecting people with weakened immune systems or generally poor health. Acanthamoeba spp also cause amoebic keratitis – a rare corneal infection that can lead to blindness in severe cases, and in the United States the condition is most often associated with improper contact lens use.

Despite the poor prognosis of these two emerging infectious diseases, their rarity has made them “orphan” diseases with no concerted efforts to discover new drugs to treat them, Dr. Kyle said.

“The major problem for infections caused by any of the pathogenic free-living amoeba is the lack of effective treatments,” he said. “PAM and GAE are usually fatal diseases even if the infection is diagnosed promptly and treated with the best available drug regimens.”

Watch a video about how to prevent Naegleria fowleri’s deadly infection:

//www.youtube.com/watch?v=m8aNlHISonQ

-USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences; and the USF Physicians Group. USF Health is an integral part of the University of South Florida, a high-impact, global research university dedicated to student success. For more information, visit health.usf.edu.

Potent compound inhibits protein synthesis at various stages of malaria parasite’s life-cycle

With the rapid emergence of multi-drug resistant strains of malaria, the need to find new drugs capable of delaying or preventing drug resistance has become even more urgent.

Now, an international team of researchers – including two from the University of South Florida – has discovered a promising new antimalarial drug that inhibits the production of a protein involved in the replication and transmission of the malaria parasite.  If successfully developed, the new drug working in combination with an existing fast-acting antimalarial may be less likely to develop rapid resistance to major strains of malaria parasites.

Dennis Kyle, PhD, Distinguished University Health Professor, and Anupam Pradhan, PhD, a research associate, both from the USF College of Public Health Department of Global Health, were among the co-authors of the multisite preclinical study published June 18 in the journal Nature.  The study was led by researchers at the University of Dundee Division of Biological Chemistry and Drug Discovery.

Dennis Kyle, PhD

The USF researchers demonstrated in a mouse model of malaria that the new drug candidate, known as DDD107498, helped block the spread of the parasitic disease with greater effectiveness than current antimalarial combination drugs. Their work was supported by a grant from Medicines for Malaria Venture.

In various preclinical studies the potent drug proved highly effective and safe while demonstrating a broad spectrum of antimalarial activity against several life-cycle stages of the malaria parasite Plasmodium falciparum.  This ability to kill parasites without harmful or bothersome side effects at all stages of a complex malaria lifecycle – after the parasites enter the bloodstream through the bite of bloodstream, once they infect the liver and as soon as the modified parasites emerge from the liver to attack red blood cells – will be critical in eradicating malaria.

DDD107498 also has the potential to be administered in less costly single doses (approximately $1 per treatment) – a major advantage since the mosquito-borne disease most often affects poor people living in developing countries, particularly children and pregnant women.

Anupam Pradhan, PhD

The researchers found that DDD107498 works by blocking a molecular target identified as translation elongation factor 2 (eEF2), which is essential for protein synthesis and expressed in various life cycle stages of malaria. Its high potency and long half-life may be well suited for both preventing malaria and offering long-term protection against re-infection.

“The discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery,” the authors concluded.

Article citation:
“A novel multiple-stage antimalarial agent that inhibits protein synthesis,” Beatriz Baragaña, Irene Hallyburton, Marcus C. S. Lee, Neil R. Norcross, Raffaella Grimaldi, Thomas D. Otto, William R. Proto, Andrew M. Blagborough, Stephan Meister, Grennady Wirjanata, Andrea Ruecker, Leanna M. Upton, Tara S. Abraham, Mariana J. Almeida, Anupam Pradhan, Achim Porzelle, María Santos Martínez, Judith M. Bolscher, Andrew Woodland, Suzanne Norval, Fabio Zuccotto, John Thomas, Frederick Simeons, Laste Stojanovski, Maria Osuna-Cabello, Paddy M. Brock, Tom S. Churcher, Katarzyna A. Sala, Sara E. Zakutansky, María Belén Jiménez-Díaz, Laura Maria Sanz, Jennifer Riley, Rajshekhar Basak, Michael Campbell, Vicky M. Avery, Robert W Sauerwein, Koen J. Dechering, Rintis Noviyanti, Brice Campo, Julie A. Frearson, Iñigo Angulo-Barturen^, Santiago Ferrer-Bazaga, Francisco Javier Gamo, Paul G. Wyatt, Didier Leroy, Peter Siegl, Michael J. Delves, Dennis E. Kyle, Sergio Wittlin, Jutta Marfurt, Ric N. Price, Robert E. Sinden, Elizabeth Winzeler, Susan A. Charman, Lidiya Bebrevska, David W. Gray, Simon Campbell, Alan H. Fairlamb, Paul Willis, Julian C. Rayner, David A. Fidock, Kevin D. Read, and Ian H. Gilbert; Nature, 522, 315-320, 18 June, 2015;  doi:10.1038/nature14451

Tampa, FL (Jan. 28, 2015) – A University of South Florida Health College of Public Health professor and his team of researchers have zeroed in on compounds that could one day lead to fast-acting treatments for the fatal infection caused by the brain-eating amoeba known as Naegleria fowleri.

In a study published online this month in the  journal Antimicrobial Agents and Chemotherapy, Dr. Dennis Kyle and his fellow researchers show that the two new compounds they identified were 500 times more potent than drugs currently used to combat the amoeba’s fatal infection.

From left: Lead authors Christopher Rice, PhD, postdoctoral fellow, and Beatrice Colon, PhD student, with the study’s principal investigator Dennis Kyle, PhD.

Naegleria fowleri, a free-living amoeba (or FLA) commonly found in warm freshwater lakes, ponds and rivers, hot springs, and poorly chlorinated pools, causes primary amoebic meningoencephalitis, or PAM. PAM is a disease that though rare, is almost always deadly. With a 97 percent fatality rate, the disease usually affects summertime swimmers or Neti pot users who get contaminated water up their noses. (They cannot get PAM by swallowing or digesting contaminated water because stomach acid kills the amoeba.)

Once in the nose, the amoeba quickly moves to the brain, where the resultant infection destroys brain tissue, often leaves afflicted patients comatose within days and usually kills them in a little more than a week. Of 132 reported cases in the United States through 2013, only three survived, according to the Centers for Disease Control and Prevention. The most recent U.S. death was that of a 9-year-old Kansas girl, an avid water skier who died last summer from PAM after swimming in several area lakes.

Despite PAM’s dire prognosis, its rarity has made it an “orphan disease” – with no concerted efforts to discover new drugs to treat people affected by it, said Dr. Kyle, a professor of global health in the USF College of Public Health.

“One of the major problems is that there have been few people working on it,” he added.

Dr. Kyle had studied Naegleria fowleri as a Ph.D. student. In the decades that followed, his expertise and specialization took him elsewhere into antimalarial drug research and to prominent national and international positions – including as deputy director of the Division of Experimental Therapeutics for the U.S. Army’s Drug and Vaccine Development Programs; and also as the chair of the Genomics and Discovery Research Steering Committee and the Compound Evaluation Network for the World Health Organization.

During those years, he kept up with findings related to the amoeba. He became perplexed as to why modern drug discovery methods were not being applied to this organism.

In this study, Dr. Kyle did just that, assisted by a team of researchers that included Dr. David Boykin from Georgia State University, who worked closely with Dr. Kyle and was the lead on medicinal chemistry aspects of the project.

The brain-eating amoebae Naegleria fowleri as seen under a microscope, magnified 400 times.

The study – which was supported by a grant from the National Institute of Allergy and Infectious Diseases – outlines how they developed for the first time the screening tools used to identify chemical compounds with the potential to treat the disease.

Up to this point, drugs used against PAM – including Amphotericin B, pentamidine, propamidine, anticancer miltefosine and azoles – were developed to tackle other diseases but were also found to have a limited impact on the amoeba. Yet no large-scale drug screening program existed to address it head-on.

“In this study, we aimed to develop a discovery paradigm to identify, evaluate, optimize, and advance new molecules towards the clinic for use as new therapies for pathogenic FLA,” the researchers wrote in the study’s report.

A new 72-hour assay or measurement format they developed revealed the lack of potency and slow onset of most drugs currently used against the amoeba. In a major breakthrough, the new format and tools instead helped them discover compounds with 500 times the potency and ways to isolate compounds that take action far faster than current treatments.

Given the deadly speed of the amoeba’s destruction, this last part becomes essential, Dr. Kyle said.

“We really need a new drug that acts quickly,” Dr. Kyle added.

To be sure, Dr. Kyle does not anticipate the studies’ findings to one day supplant current therapy or treatment for PAM, but rather to enhance and complement it.

Also, the research appears promising for future treatment against other types of related amoebae not connected to PAM, such as the one that causes Acanthamoeba keratitis, a serious eye infection that can result in visual impairment or blindness.

Still, more research is needed before new drugs hit the market, Dr. Kyle stressed. That includes more testing of compounds to make sure they cross the blood-brain barrier, the testing on genetic mouse models and clinical trials before seeking Food and Drug Administration approval.

“There is work to do,” he said. The end goal is to save more lives.

“That’s certainly our hope,” he said, “to reduce the fatalities.”

                                                                                                                                                            -USF Health-
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation.  For more information, visit www.health.usf.edu

News release by Saundra Amrhein

Media contact:
Anne DeLotto Baier, USF Health Communications
abaier@health.usf.edu or (813) 974-3303

Tampa, FL (March 20, 2013) — University of South Florida researchers played a key role in an international multidisciplinary project that has yielded a promising new antimalarial drug with the potential to cure the mosquito-borne disease and block its transmission with less costly,  low doses.

Roman Manetsch, PhD, USF associate professor of chemistry, and Dennis Kyle, PhD, USF professor of global health, were co-leaders of the USF team, which helped to discover and develop a series of potent compounds to combat malaria known as the 4-(1H)-quinolone-3-diarylethers, or quinolones.

The USF researchers were part of larger Medicines for Malaria Venture (MMV) project team including Oregon Health & Science University in Portland, Drexel University in Philadelphia, and Monash University in Australia.

Dennis Kyle, PhD, professor of global health at the USF College of Public Health, is a technical advisor to the Medicines for Malaria Venture team preparing the new antimalarial drug ELQ-300 for clincal trials.

The researchers narrowed the most effective drug candidates in the quinolones series to one lead drug – ELQ-300 – now moving toward clinical testing.

The project team’s findings are published today in the journal Science Translational Medicine.  Alexis N. LaCrue, PhD, a research associate in Dr. Kyle’s laboratory, was a co-first author for the paper along with Aaron Nilsen, PhD, of Portland VA Medical Center.

In initial preclinical tests, the lead drug demonstrated impressive preventive and transmission-blocking – and a low likelihood for developing rapid resistance to major strains of malaria parasites.

In addition, ELQ-300 could likely be produced more cheaply than existing antimalarial drugs – a major advantage in treating a tropical disease that kills nearly one million people a year and causes recurring bouts of severe and incapacitating illness, most often among poor people in developing countries.

“This is one of the first drugs ever to kill the malaria parasite in all three stages of its life cycle,” said Dr. Kyle, a member of the Global Infectious Diseases Research team at the USF College of Public Health.  “So, it may become part of a new-generation therapy that not only treats sick people and prevents them from getting ill, but also blocks the transmission of malaria from mosquitoes to humans … If the drug can break the parasite life cycle, we may ultimately eradicate the disease.”

New life from an old class of compounds

The new drug class identified by the researchers were derived from the first antimalarial quinolone, endochin, discovered more than 60 years ago but never pursued as a treatment because it appeared not to work in humans.

Using new technology to optimize the quinolones, the MMV project team demonstrated that these compounds were indeed highly effective against Plasmodium falciparum, the most lethal strain of malaria, and Plasmodium vivax, the major cause of malaria outside Africa.  The quinolones target both the liver and blood stages of the parasite as well as the forms critical for disease transmission.

“This was a very challenging project requiring years of hard work, collaboration across disciplines, and a good portion of luck,” said Dr. Manetsch, whose laboratory specializes in medicinal chemistry, drug discovery and development of novel chemical probes to characterize drug-protein interactions.

Alexis LaCrue, PhD, a research associate at the USF Department of Global Health, Tampa, FL, was a co-first author for the Medicines for Malaria Venture paper detailing a series of potent compounds active against all three stages of the malaria parasite life cycle.

Optimizing drug success against a complex parasite life cycle

In humans, the malaria parasite targets the liver after it enters the bloodstream through the bite of an infected mosquito.  Once inside the liver, the infecting parasites for most types of malaria multiply and rupture liver cells, escaping back into the bloodstream — although sometimes parasites can remain dormant in the liver for extended periods. The parasites, now modified to attack red blood cells, rapidly create more parasites, which spread throughout the bloodstream in waves.

The researchers needed to find and fine-tune a drug with a long half-life both to prevent malaria and to offer long-term protection against reinfection.

“It was a balancing act to optimize an antimalarial drug so that it was soluble and metabolically stable, without compromising its potency,” Dr. Manetsch said.  “We wanted a compound that within an individual would not break down too quickly, remain circulating in the blood for a long enough period to kill the parasites, and be highly active in blocking transmission in rodent models of malaria.”

The antimalarial drug developed needed to be potent enough to work without harmful or bothersome side effects.

ELQ-300 targets a protein complex of the mitochondria that is integral for the energy household of a cell, Dr. Manetsch said.   That’s good when you’re trying to incapacitate a malaria parasite’s powerhouse, but the same hit in a human’s mitochondria could be disastrous, he added.

So, Dr. Manetsch, with the help of Dr. Kyle’s expertise in parasitology, structurally modified the quinolone scaffold so that the drug candidate ELQ-300 would selectively hit only the malaria parasite’s target while sparing the human mitochondria.

Roman Manetsch, PhD, associate professor of chemistry, was co-leader, along with Dr. Kyle, of the USF team that helped to discover and develop a series of potent compounds (quinolone-3-diarylethers)to combat malaria.

Antimalarial drug resistance: A global health threat

With the rapid emergence of multi-drug resistant strains of malaria, the need to find new drugs capable of delaying or preventing drug resistance has become even more pressing, researchers say.

The quinolones, including ELQ-300, target the same biological pathway as atovaquone, the main component of Malarone, one of the newest combination drugs used to treat malaria. But, in repeated experiments ELQ-300 did not generate drug-resistant strains of the malaria parasite – making it a significant improvement over atovaquone.

In addition, the new drug’s design makes it more effective at lower doses, hopefully meaning fewer and smaller pills for patients at a lower cost, said Dr. Kyle, a technical advisor for the MMV team preparing ELQ-300 for clinical trials.

Dr. Kyle and Dr. Manetsch, funded by National Institutes of Health grants totaling more than $2.5 million, continue to collaborate on research to identify and develop novel antimalarial drugs.

Article citation:
“Quinolone-3-Diarylethers: A New Class of Antimalarial Drug,” Aaron Nilsen, Alexis N. LaCrue, Karen L. White, Isaac P. Forquer, Richard M. Cross, Jutta Marfurt, Michael W. Mather, Michael J. Delves, David M. Shackleford, Fabian E. Saenz, Joanne M. Morrisey, Jessica Steuten, Tina Mutka, Yuexin Li, Grennady Wirjanata, Eileen Ryan, Sandra Duffy, Jane Xu Kelly, Boni F. Sebayang, Anne-Marie Zeeman¹, Rintis Noviyanti, Robert E. Sinden, Clemens H. M. Kocken, Ric N. Price, Vicky M. Avery, Iñigo Angulo-Barturen, María Belén Jiménez-Díaz, Santiago Ferrer, Esperanza Herreros, Laura M. Sanz, Francisco-Javier Gamo, Ian Bathurst, Jeremy N. Burrows, Peter Siegl, R. Kiplin Guy, Rolf  W. Winter, Akhil B. Vaidya, Susan A. Charman, Dennis E. Kyle, Roman Manetsch, and Michael K. Riscoe; Science Translational Medicine, Vol. 5, Issue 177.

-USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities. For more information, visit www.health.usf.edu

Media contact:
Anne DeLotto Baier, USF Health Communications
(813) 974-3303 or abaier@health.usf.edu

Six years ago USF had no researchers working on malaria.   Today, more than 60 faculty members, staff and students are tackling major challenges needed to end malaria, a preventable and treatable mosquito-borne disease that killed more than 650,000 people last year — overwhelmingly children in sub-Saharan Africa

That accomplishment didn’t escape the notice of the Malaria Policy Center in Washington, DC.   The center invited Dennis Kyle, PhD, professor of global health in the USF College of Public Health, to showcase USF’s malaria research at a Capitol Hill expo attended by legislators, Congressional staff, and members of the global health community on World Malaria Day (April 25).

Dr. Kyle was among 20 top malaria researchers from  U.S. companies, universities and research institutions brought together to highlight domestic innovation, economic development, and the scientific and technological progress achieved in the fight against malaria. Other presenters included representatives from Johns Hopkins University, the Harvard Malaria Initiative, Emory University, Draper Laboratory, Virginia Tech, and Fraunhofer USA Center for Molecular Biotechnology.

Dr. Dennis Kyle

Dr. Kyle gave expo attendees gathered in the Russell Senate Office Building an overview of USF’s progress in malaria research.

The USF global infectious disease research team has successfully cultivated drug-resistant malaria parasites from Cambodia in the laboratory – a much needed in vitro model to help determine how the parasite builds up tolerance to artemisinin combination therapy, a mainstay malaria treatment, he said.

The USF team is also working with Draper Laboratory tissue engineering experts, creating advanced devices to accelerate discovery of new therapies for malaria and its prevention.

A recent USF collaboration with the Medicines for Malaria Venture has yielded a new series of compounds that offer promise in attacking malaria on several fronts — by blocking the dormant liver stages of parasite development, killing the blood stages, and also preventing transmission from human to the mosquito.  The disease is transmitted to humans through the bite of an infected mosquito.

“The University of South Florida is active in many major research areas currently required to tackle the problem of eliminating malaria,” Dr. Kyle said. “We were able to build a world-class effort in malaria research through key investments in the university’s College of Public Health and state funding for both a Center of Excellence for Drug Discovery and Innovation and a World Class Scholars Program.”