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Category: CTEGD Blog

Stronger treatments could cure Chagas disease

3D (left) and single slice (right) light sheet microscopy imaging of the heart of a mouse infected with two strains (red and blue) of Trypanosoma cruzi. (Image credit: Fernando Sanchez-Valdez)

Research shows stronger but less frequent drug doses could be key

Researchers in the University of Georgia’s Center for Tropical and Emerging Global Diseases have found that a more intensive, less frequent drug regimen with currently available therapeutics could cure the infection that causes Chagas disease, a potentially life-threatening illness affecting up to 300,000 people in the United States.

Trypanosoma cruzi is a single-celled parasitic organism that causes Chagas disease. At least 6 million people are infected by T. cruzi, mostly in South America. Current drug therapies have been ineffective in completely clearing the infection and are associated with severe adverse side effects.

A single dose of benznidazole has been shown to be highly effective in killing more than 90% of parasites. However, after a CTEGD team found some of the parasites enter into a dormancy stage, the researchers hypothesized that an intermittent treatment schedule could be effective.

Rick Tarleton
Photo credit: Peter Frey/UGA

“Current human trials are only looking at giving lower doses over a shorter time period, which is the exact opposite of what we show works.”  — Rick Tarleton

“In this system we can see what a single dose of drug does,” said Rick Tarleton, Regents’ Professor in UGA’s department of cellular biology. “Does it make sense to give a drug twice daily when the remaining dormant parasites are insensitive to it?”

The investigators found that giving as little as two-and-a-half times the typical daily dose of benznidazole, once per week for 30 weeks, completely cleared the infection, whereas giving the standard daily dose once a week for a longer period did not.

“Current human trials are only looking at giving lower doses over a shorter time period, which is the exact opposite of what we show works,” said Tarleton.

Since Tarleton’s team worked with a mouse model, how this change in treatment regimen will translate in humans is yet unknown, as are any potential side effects of the higher doses. Adverse reactions already are a problem with current treatments; the hope is that side effects from a less frequent dosage would be more tolerable.

Significant challenge

Assessing the success of treatments in Chagas disease is a significant challenge. Tissue samples from infected organisms might not be representative of the entire organ or animal, since low numbers of persistent, dormant parasites can be difficult to detect. Therefore, Tarleton’s group used light sheet fluorescence microscopy to view intact whole organs from infected mice.

“With light sheet fluorescence microscopy, you have a broad view of potentially any tissue in the mouse that allows for dependable assessment of parasite load and persistence,” said Tarleton. “It gives you an incredible view of the infection.”

Using this technology, they learned something new about the dormant parasites: Some were still susceptible to drug treatment. This provides hope that new drug therapies could be developed to target these parasites.

“Discovery of new drugs should continue,” Tarleton said. “We still need better drugs.”

 

Co-led by assistant research scientist Juan Bustamante and research professional Fernando Sanchez-Valdez in Tarleton’s research group, the study’s findings appear in Science Translational Medicine.

 

 

Dennis Kyle: Finding Solutions for Deadly Diseases

Dennis Kyle
Dennis Kyle leads the UGA Center for Tropical and Emerging Diseases, and his endowment enables him to run a 16-person lab of student researchers, postdocs, and research scientists fighting a host of parasitic diseases around the world. (Photo by Andrew Davis Tucker/UGA)

GRA Endowment helps researchers save lives through drug discovery

The Amoeba Summit in Orlando last year is where the importance of her work on drug discovery for deadly amoebae really hit home for Cassiopeia Russell.

It was there she learned the story of an 11-year-old boy who had gone on a family vacation to Costa Rica and was having a great time going down a waterslide at a hot spring there. Days later, he started complaining of a terrible headache. Then he started vomiting. Within a week, he was dead. The cause was a microscopic organism, Naegleria fowleri, living in the warm waters of the spring.

Cassiopeia Russell
Cassiopeia Russell is a doctoral student working in Dennis Kyle’s lab on treatments to combat Naegleria fowleri, a rare but deadly brain-eating microscopic organism that can be 99% fatal if contracted. “This parasite infects mainly young children,” she says. “Hundreds have died.”

Russell, a doctoral student, had been working in the lab of Dennis Kyle, director of the UGA Center for Tropical and Emerging Global Diseases, for about a year when she was able to attend the conference thanks to a Georgia Research Alliance (GRA) endowment and learn how the research she does in the lab is making a real impact on people’s lives. The GRA was founded with the goal of expanding Georgia universities’ ability to conduct high-level research with the potential of bringing new and innovative products to market. Kyle is the GRA Eminent Scholar in Antiparasitic Drug Discovery, and his endowment enables him to run a 16-person staff of student researchers, postdocs, and research scientists.

“I asked myself at the beginning if I really wanted to work on a parasite this rare,” Russell says. “But if you look at the statistics, this parasite infects mainly young children. Hundreds have died.” She thinks about that every day in the lab.

More commonly referred to as the brain-eating amoeba, Naegleria fowleri is a surprisingly common amoeba found in warm water lakes, ponds, and rivers. When water is forced up the nose—like when diving into a body of water or repeatedly riding a waterslide—the parasite travels to the brain, where it attacks the organ’s cells. Though infections are rare, the brain-eating amoeba kills almost everyone it infects.

One reason Naegleria fowleri is so deadly is because symptoms of the infection resemble those of viral meningitis, a much more common and more treatable disease. “That misdiagnosis and waiting to see if the patient gets better after beginning treatment is wasting valuable time,” says Russell. She’s committed to finding faster, more effective ways to diagnose the condition so patients can get the right medications in time to stop the disease’s progression.

The Georgia Research Alliance really helped me set up this whole operation when I got here. Without the GRA, there’s no way that I could have had this team going for three years.” — Dennis Kyle, GRA Eminent Scholar in Antiparasitic Drug Discovery

As a member of Kyle’s lab, Russell also tests drug compounds to see which ones can kill an amoeba without destroying the human cells it infects. Current drugs used to treat the infection aren’t very effective and are highly toxic.

Despite being almost 99% fatal, not many federal dollars go toward research on brain-eating and other kinds of amoebae. That’s where the Georgia Research Alliance comes in.

“The Georgia Research Alliance really helped me set up this whole operation when I got here,” says Kyle. “Without the GRA, there’s no way that I could have had this team going for three years. This is something that we have concerns about in Georgia. Every summer, we hear of Naegleria fowleri cases on the news. But we don’t have many people worldwide working on it and very few doing the drug discovery needed to come up with a new drug that could save lives. And that’s really our goal.”

The other main area of research in the Kyle lab is malaria and how the parasite becomes resistant to the drugs commonly used to treat it. Additionally, a less commonly studied strain of malaria can go dormant inside its host, effectively hiding in the liver until flaring up weeks, months, or even years later. Kyle and his team were able to develop a model that simulates that dormant phase to test a variety of drugs to find a way to kill the parasite.

But in order to use that model, researchers in the lab must collect parasites from the field. The endowment helped the lab send assistant research scientist Steven Maher to Asia 25 times over the past four years to work with partners in Cambodia and Thailand.

“International travel has definitely changed my life,” Maher says. “Right now, we’re supporting people in Asia and their families, and I think having that human connection is really important. I think all too often we do research and we forget about ‘how is what I’m doing helping real people?’ I think a lot of researchers would benefit from that type of experience.”

The Georgia Research Alliance, private donors, and the UGA Athletic Association are committed to providing researchers like Russell and Maher with opportunities to advance their work on deadly infectious diseases threatening nations around the world.

Steven Maher with Cambodian colleagues
Assistant research scientist Steven Maher (far right) with the team he works with in Cambodia. GRA funding has allowed him to travel to Asia 25 times over the past four years battling malaria.

 

This article was originally published at https://news.uga.edu/dennis-kyle-finding-solutions-for-deadly-diseases/

Trainee Spotlight: Melissa Sleda

Melissa Sleda

 

Melissa Sleda, a Ph.D. trainee is Silvia Moreno’s laboratory, is in her third year at UGA. She is originally from Sandusky, Michigan and attended Lawrence Technological University where she majored in Molecular and Cell Biology with a minor in Chemistry. At UGA, she has held positions as the Secretary for the Cell Bio Grad Student Association (2019-2020), and as Treasurer (2019-2020) and current President (2020-2021) of the CTEGD grad student association.

Melissa Sleda has been awarded a T32 Trainee Fellowship for the 2020-2021 academic year.

Why did you choose UGA?

I chose UGA because of the Integrated Life Sciences Umbrella program. As an incoming graduate student, I was not set on studying a particular organism, and I was excited for the opportunity to rotate in labs across different departments.

What is your research project?

My project seeks to characterize enzymes of the isoprenoid biosynthetic pathway in Toxoplasma gondii and to investigate these enzymes as potential chemotherapeutic targets. The current chemotherapy for Toxoplasmosis is ineffective because it does not eliminate the chronic stage of infection. My project seeks to test drugs that target enzymes of the isoprenoid pathway in both the acute and chronic forms of infection in order to find a more effective chemotherapy.

What are your future professional plans?

My future career goal is to stay in academia and become a professor at a smaller institution with a higher emphasis on teaching and leading smaller research projects. I want to help students at smaller universities gain research experience through classroom labs and one-on-one research projects.

What do you hope to do for your Capstone Experience?

For my capstone experience, I hope to be able to do research in another country to gain a wider perspective of how research is done in other countries. I hope that I am able to do research in a lab that I can learn new techniques that will translate into my research project.

What is your favorite thing about Athens?

My favorite thing about Athens is the warm weather and the great sense of community.

What advice do you have for students interested in this field?

Do things out of your comfort zone because it will help you develop as a scientist.

 

Support trainees like Melissa by giving today to the Center for Tropical & Emerging Global Diseases.

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Trainee Spotlight: Alona Botnar

Alona Botnar

T32 trainee Alona Botnar is entering her fifth year as a Ph.D. candidate in Dr. Dennis Kyle’s laboratory. She is from Doylestown, Pennsylvania and completed her B.S. in Chemistry with a minor in Biochemistry at the University of Georgia in 2015. During her undergraduate career, she also worked at Janssen, a pharmaceutical company of Johnson & Johnson as a Biologics R&D co-op.

As a graduate student, she was able to spend three semesters teaching Anatomy and Physiology labs here at UGA, and in 2019, she was awarded the Outstanding Teaching Assistant Award sponsored by the Office of the Vice President for Instruction. She also received a graduate school travel award to attend the 2018 annual meeting of the American Society of Tropical Medicine and Hygiene in New Orleans, Louisiana, and an Office for Vice President and Research travel award to attend the 2020 Molecular Approaches to Malaria meeting held in Lorne, Victoria, Australia.

Why did you choose UGA?

Having been at UGA for my undergraduate degree, I was already in love with UGA and Athens and all that they have to offer. I was attracted to the Integrated Life Sciences program because it gives incoming graduate students the freedom to explore a wide range of research topics among 14 different departments before choosing the lab they would ultimately like to join. Furthermore, I found the interdisciplinary approach of the program appealing. I love the Center for Tropical and Emerging Global Diseases because of all the resources available to us as scientists. Not only do we have state of the art microscopy and flow cytometry cores, but we also have very collaborative labs that are happy to share equipment, supplies, and expertise.

What is your research focus?

My research is focused on malaria and addressing significant problems at the stages of development at which the malaria parasite enters a drug-induced dormant period and evades the antimalarial. The mechanism by which the parasite enters drug-induced dormancy and later recrudesces to continue development is currently unknown.

Half the world’s population is at risk of malaria with about half a million people dying each year from it. A majority of these deaths are in children under the age of 5, located mainly in sub-Saharan Africa. While there are 5 species that can infect humans, Plasmodium falciparum is the most lethal and is responsible for a majority of the deaths. Our current arsenal of malaria drugs is failing at an alarming rate as drug-resistant strains of the parasite continue to emerge.

Thus I chose this research project because it is vital that we respond to the challenge of antimalarial drug resistance by not only developing novel drugs but also by understanding the mechanisms the parasite is using to evade the drugs.

What are your future career goals?

I plan on continuing my work in the field of infectious diseases. I am leaning towards industry research but I’m keeping an open mind. Lately, I have been interested in alternative careers available to life science Ph.D.’s such as consulting and being a medical science liaison.

What is your favorite thing about UGA?

UGA football. There’s nothing quite like a fall Saturday in Athens between the hedges. GO DAWGS!

Do you have any advice for a student interested in this field?

It’s never too early or too late to get into the field. Don’t be afraid to send those emails and get involved in research. And always ask questions.

 

Support trainees like Alona by giving today to the Center for Tropical & Emerging Global Diseases.

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Age influences thermal tolerance in Asian malaria mosquito

Environmental portrait of Courtney Murdock in her laboratory at UGA’s School of Veterinary Medicine (Dorothy Kozlowski)

Malaria disease transmission models are important tools for controlling and eliminating disease spread. However, a model is only as good as the assumptions about the various variables. Dr. Courtney Murdock, a member of the UGA’s Center for Tropical and Emerging Global Diseases and professor at Cornell University, has been studying how various biological and environmental factors influence mosquito survival. In a study recently published in the Proceedings of the Royal Society B led by graduate student Kerri Miazgowicz, Murdock and her colleagues examined several life traits, such as biting, feeding, and egg production, over the course of the life span of the mosquito Anopheles stephensi in hopes of providing better data for the models.

“Due to a lack of high-quality entomological data in general, researchers are often forced to input data from multiple disease systems to inform models in a given system or use approximations of key model components,” said Murdock.

An. stephensi is the primary mosquito species that transmits malaria in India. While most of the focus on malaria is most often associated with sub-Saharan Africa, it is widespread in the Indian subcontinent and throughout southeast Asia. Several Plasmodium species cause malaria, but P. falciparum is the deadliest of them. It has also shown drug resistance to current treatments. Control of the mosquito population is an important component in malaria control and elimination programs. Researchers need to be able to more accurately predict where mosquito populations will occur as climate changes and current territories become unsuitable living and breeding grounds. Program managers need to be prepared to incorporate more northern regions in their control efforts.

trainee field work
Kerri Miazgowicz, a graduate student in the Murdock Laboratory at the University of Georgia, led the study on the effects of age on thermal tolerances.

Current models rely on data that are only snapshots in time and often from multiple mosquito species, particularly the African mosquitoes, which are vectors for different malaria species. Miazgowicz, Murdock, and colleagues wanted to determine if the data from a single species of mosquito and parasite, over the course of its entire lifespan, significantly influenced current models in determining disease transmission in hopes of creating more accurate models.

The single most important factor driving current models is temperature. Mosquitoes are cold-blooded animals and therefore rely on their environment to regulate their body temperature. However, temperature is not the only factor influencing life traits. Currently, data are only available as snapshots in time. These incomplete data do not take into account for changes in mosquito behavior and life traits that occur over the course of the mosquito’s life. Murdock and her colleagues have recorded changes in biological function as the mosquito ages. Just as people slow down biologically as they age – metabolism slows, reproduction ability declines, etc. – the same is true for mosquitos. They also found that various traits peak at different times depending on temperature. Importantly they found that temperature and age significantly affected the number of females taking a blood meal (this is the means in which malaria parasites are transmitted to humans) on a given day, average daily egg production, and ultimately survival.

The findings in this study indicated that the addition of An. stephensi data yielded qualitatively different temperature-transmission suitability relationships compared to models that included multiple malaria vectors. With An. stephensi data, the model predicted a broader geographical range of temperature suitability.

“Accounting for these age and species effects in models of transmission potential alters how much of South Asia is predicted to be suitable for malaria relative to models that do not account for these factors,” said Murdock.

These findings can lead to improved malaria transmission models. However, more study outside the laboratory is needed to truly understand the impact mosquito age has on life traits and thermal tolerance.

“This study highlights a critical need for more research in natural settings characterizing the effects of age on mosquito biology to improve predictions of current and future risk,” concluded Murdock.

 

NIH awards CTEGD $1.9 million to support training in tropical and emerging global diseases

UGA’s Center for Tropical and Emerging Global Diseases has been awarded $1.9 million from the National Institutes of Health to continue its pre- and post-doctoral training program for the next five years. First funded in 2004, CTEGD has received nearly $2 million from NIH to train the next generation of scientists in the fight against neglected tropical diseases. The new funding will support additional fellowships and new training initiatives.

Every year, parasitic diseases are responsible for more than a million deaths and leave hundreds of millions more with chronic infections lasting years. However, there are few U.S. programs that specifically train researchers in this field.

CTEGD is recognized as a pre-eminent research center that brings together the largest number of laboratories in the U.S. to study the full gamut of parasitic diseases, which are highly prevalent in sub-Saharan Africa, South America and Asia. Often, these diseases are the consequence and cause of poverty, and they are increasingly emerging (or re-emerging) in industrialized nations. Most of these diseases have no cure and few treatment options, and growing drug resistance complicates the fight against them. Now more than ever, researchers are needed in the field of parasitology and tropical diseases in order to improve global health.

NIH recognizes the need for researchers trained in parasitology and tropical disease, as well as UGA’s and CTEGD’s ability to fill it, by providing funding for two additional pre-doctoral fellowships. CTEGD will now be able to award five pre-doctoral fellowships and two post-doctoral fellowships each year

“This is incredibly exciting,” said Dr. Silvia Moreno, program director of CTEGD’s Training in Tropical and Emerging Global Diseases (TTEGD) and Distinguished Research Professor in cellular biology. “It’s a very competitive program and having additional pre-doc positions funded is even more exciting. Our program offers a great environment for training in parasitology which is the result of the hard work of the CTEGD community plus great UGA institutional support”.

The support of the university community

UGA’s support of the program has been instrumental to its continuing funding by NIH. The state-of-the-art equipment and facilities available to trainees allow them to learn cutting-edge techniques and technologies.

Under the direction of Vice President David Lee, the Office of Research has committed significant support over the next five years to fund the capstone experience, which allows each fellow to conduct research in an international setting, and two additional pre-doctoral assistantships.

“The Center for Tropical and Emerging Global Diseases is one of the key components of UGA’s strength in the wide-ranging fight against human disease,” Lee said. “The exceptional training that students and posdocs receive at CTEGD is a point of significant pride for the university, and I am committed to supporting the further growth of the Center and the TTEGD program.”

The Office of Postdoctoral Affairs will continue to partner with CTEGD to provide grant-writing workshops and career development opportunities for post-doctoral fellows. Last year, CTEGD organized a workshop on NIH’s K-Award grants that are available to post-doctoral fellows.

Franklin College of Arts & Sciences has also committed over the next 5 years to match funds from CTEGD to provide for a mini-sabbatical program a faculty member from a local college or university, along with up to two undergraduate students from that school, to spend a semester working in a CTEGD laboratory. The goal of this program is to increase awareness of post-undergraduate opportunities and spark interest in neglected tropical disease research.

Committed to training the next generation of scientists

To date, 37 pre- and post-doctoral fellows have received training support through the NIH T32 Training Grant. The fellowships awarded by CTEGD include a stipend, travel award, health insurance, and some financial support for research supplies. Pre-doctoral fellows also receive a tuition waiver. In the past 15 years, graduate students have assisted in field studies in Haiti, Tanzania, Argentina, Thailand, Ecuador, and Kenya as part of their capstone experience.

“My trip to Ecuador was unimaginably enriching,” said Dr. Manuel Fierro, a former T32 fellow who completed his Ph.D. this year. “I was presented with the way great research is done in a setting containing fewer resources than in the US and it gave me important connections for my professional development. More importantly, it gave me hope of returning to my home country and continue applying my parasitology training.”

Trainees have gone on to positions in academia, government and industry. They have secured positions as post-doctoral fellows, staff scientists, and assistant professors at such institutions as the Centers for Disease Control and Prevention, Food and Drug Administration, the National Institutes of Health, University of California, Emory University School of Medicine, Tufts University’s Cummings Veterinary Medical School, and Wellcome Centre for Anti-Infective Research in Scotland.

Embarking on its 16th year this fall, CTEGD is committed as ever to increasing rigor, diversity, and career development in its training program. New requirements for post-doctoral trainees, more rigorous training for new trainers, strategic recruitment initiatives to target underrepresented minorities, and expansion of training to include large data mining and computer science are just a few of the changes the program will undertake over the next five years.

“The T32 training grant represents the core of CTEGD’s effort to prepare the next generation of scientists to tackle the scourge of the neglected parasitic diseases of mankind,” said Dr. Dennis Kyle, director of CTEGD. “The renewal of this award allows us to expand our efforts and is recognition of the excellence of our students, postdocs, staff, and faculty.”

Trainee Spotlight: Emma Troth

Emma Troth

Emma Troth, a Ph.D. trainee in Dennis Kyle‘s laboratory, is entering her fourth year at UGA. She is originally from Eureka, Illinois, and attended Bradley University where she majored in Biology with a minor in Ethics. While at UGA, Emma has served as president of the CTEGD Graduate Student Association (2019-2020) and is currently the CTEGD Graduate Student Association representative.

How did you get interested in neglected tropical diseases?

As an undergraduate, I participated in a Research Experience for Undergraduates program at the University of Notre Dame. At Notre Dame, I worked on a project characterizing malaria vectors in the Solomon Islands and Indonesia. My summer at Notre Dame sparked my interest in neglected tropical diseases.

Why did you choose UGA?

I chose UGA because of the diversity of research. Coming into graduate school, I knew I was interested in infectious diseases but did not have my heart set on a particular organism to work on. UGA works on the biggest selection of infectious organisms. With the Integrated Life Sciences Program, I had the opportunity to experience multiple labs working on different organisms, regardless of department, to help me identify where I would like to complete my doctoral degree.

What is your research focus? Why are you interested in this topic?

My project focuses on drug discovery for Naegleria fowleri, the brain-eating amoebae. My main project focuses on structure-based drug design to develop novel drug targets against N. fowleri. Additionally, I am working to develop phenotypic drug screening assays to complement our high-throughput drug discovery. I am fascinated by N. fowleri because it is such a mysterious, deadly organism. Though infections may not be as common as other parasitic diseases, nearly all cases of primary amebic meningoencephalitis (PAM) are fatal. This amoeba is grossly understudied; very few labs in the world research this organism. It is both a privilege and a challenge to be able to work on this neglected parasite.

Have you done any fieldwork or is there a collaborator/field site that you would like to visit in order to enhance your training?

I hope to complete an internship with the Task Force for Global Health. This internship will ideally include fieldwork with one of their neglected tropical disease programs.

What are your future professional plans?

Going forward, I would like to continue my career in neglected tropical diseases with an emphasis on global health. I am particularly interested in a career involving field research. Ultimately, I hope to work for a government agency like the Centers for Disease Control and Prevention (CDC) or a non-profit organization focused on neglected tropical diseases.

What is your favorite thing about Athens?

My favorite thing about Athens is the food! There is such a variety of local restaurants and new restaurants are continually opening. Coming from a small undergraduate institution, I really enjoy the atmosphere of a large university in a small college town. Athens is a very easy city to feel “at home”.

Any advice for a student interested in this field?

Never be afraid to reach out for help, wherever you need it! Coming into graduate school can be intimidating and at times, isolating. There are so many people eager to help you on your graduate school journey and ultimately want to see you succeed. Particularly within the CTEGD, I have always been met with kind and willing responses. All it takes is for you to take the step and reach out!

Support trainees like Emma by giving today to the Center for Tropical & Emerging Global Diseases.

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SCORE – a decade of operational research with a lasting legacy

Dan Colley

It all began with a simple phone call and now, more than a decade later, the Schistosomiasis Consortium for Operational Control and Evaluation (SCORE) is preparing to pass the baton to new groups of investigators working on understanding and controlling schistosomiasis. Under the direction of Dan Colley, a member of the Center for Tropical and Emerging Global Diseases and professor emeritus of microbiology at the University of Georgia, SCORE has advanced the scientific understanding of how to control schistosomiasis and has moved us closer to the elimination of this devastating and sometimes deadly disease.

The beginning

In January 2008, Colley received a phone call from Dr. Julie Jacobson of the Bill & Melinda Gates Foundation (BMGF). She wanted Colley to lead a program on how best to control and move towards elimination of schistosomiasis. This program would not be your typical research program.

First, it would involve national Neglected Tropical Disease (NTD) programs, the World Health Organization (WHO), and others around the globe who were pursuing ways to control morbidity due to Schistosoma mansoni and S. haematobium and their transmission.

“While there were and are now many individual research programs in academia, governments and NGOs working on how to control and eliminate schistosomiasis, SCORE was somewhat different in its size and complexity, allowing it to mount large-scale studies and do so comparatively across different countries,” said Colley.

Second, the program would not focus on basic research, but the results of their research would be more directly applicable to improving national NTD control programs.

“Julie made it clear that the BMGF was not interested, at this time, in funding basic research on either anti-schistosomal drug development or anti-schistosomal vaccine development,” said Colley.

While there are several Schistosoma spp. that infect humans worldwide, this program would focus only on two species, S. mansoni and S. haematobium. Furthermore, they would focus primarily on interventions to control these infections in Africa.

With the parameters laid out and the definition of what constitutes operational research, Colley agreed to gather together a consortium of scientists and SCORE was born: their mission – to undertake operational research that could support National NTD managers in making decisions about how to best control and/or eliminate schistosomiasis in their countries.

“The vision was that research findings would be useful to the WHO in revising current and developing new guidelines on how best to control and move towards elimination of schistosomiasis,” said Colley.

Over the past decade, their mission has not changed but how they pursued that mission evolved as situations change., such as the increased availability of praziquantel, made possible through a donation of the drug by Merck, AG; a more realistic vision of the integration of NTD programs; and the desire of funders to move more quickly from control of morbidity to elimination of the disease.

The projects

Over the past decade, SCORE has pursued a number of field and laboratory-based projects in 9 African countries. Several of these studies were included in the categories of gaining control, sustaining control of schistosomiasis, or eliminating its transmission.

The control projects compared how best to deliver Mass Drug Administration (MDA) of praziquantel. Gaining control projects were focused on areas with high prevalence of infection and included research related to subtle morbidity, snail infection, and schistosome population genetics. Sustaining control project focused on areas with moderate prevalence as these areas had already achieved a level of control or simply had lower levels of prevalence.

The original focus of the elimination research project was on Zanzibar and the elimination of S. haematobium. They hoped to inform effective strategies of moving an area of low infection prevalence to total elimination of schistosomiasis. In 2013, with supplemental funding, SCORE expanded its focus on elimination research to focus on S. mansoni in Africa. However, due to conflicts within the country where this research was implemented, SCORE and partners had to withdraw. Instead, SCORE identified another elimination priority on the impact of timed interventions on seasonally transmitted schistosomiasis. This research was conducted in Cote d’Ivoire in a large area with S. haematobium.

Another group of projects focused on tools needed to evaluate control and elimination efforts. They were able to field evaluate the point-of-care circulating cathodic antigen (POC-CCA) urine assay for its use as a mapping tool for S. mansoni infection in humans. They also conducted research and evaluation on highly sensitive and specific human diagnostic tests for schistosomiasis and developed and used tools for schistosome population genetics studies.

Keeping with their mission of supporting national NTD program managers in decision-making, SCORE provided critical information by analyzing and synthesizing existing data in a series of 7 Rapid Answers Projects. Each project resulted in a 2 page brochure providing essential information on a topic of interest to program managers. These brochures are available online at https://score.uga.edu/projects/rapid-answers-project/

And finally, in order to optimize the use of the data generated in these large studies, they collected and made them accessible to the scientific community and other stakeholders. SCORE worked with database programmers and statisticians at UGA to integrate the data from various study sites and conduct analyses of combined data, while providing them to all investigators by depositing them in an open database system, ClinEpiDB.

The legacy

In July, the American Journal of Tropical Medicine and Hygiene published a supplement that summarizes many of the activities, lessons learned, and work that still needs to be done in 16 articles. This supplement is introduced with a guest editorial by N. Robert Bergquist.

Briefly the key findings and take away messages are summarized in Table 1 of the article “Contributions of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) to Schistosomiasis Control and Eliminations: Key Findings and Messages for Future Goals, Thresholds, and Operational Research” (https://doi.org/10.4269/ajtmh.19-0787).

“The impact of SCORE’s findings and messages will depend on their uptake by the WHO/NTD schistosomiasis guidelines development group in the formulation of revised and new guidelines for the control and elimination of schistosomiasis, and then whether national NTD programs consider them worthy of adoption and implementation,” said Colley.

Some of the findings from SCORE are already being implemented, such as the use of the POC-CCA rapid cassette test for mapping S. mansoni prevalence in low-to-moderate areas of schistosomiasis. Other findings, such as the occurrence of persistent hotspots in large-scale MDA programs, are now being considered by other research groups and national NTD programs.

This isn’t really good-bye

SCORE was built on the foundation of a previously BMGF-funded program – the Schistosomiasis Control Initiative (SCI). The goal of SCI, which is now a private non-governmental organization, was to determine if preventive chemotherapy, as recommended by the WHO, could be implemented countrywide to control schistosomiasis.

“It was an ambitious undertaking that SCI accomplished in multiple African countries,” said Colley. “Now knowing that with the funding, persistence, and training, MDA countrywide could be done, the BMGF decided to fund a program to compare the frequency and platforms for MDA distribution.”

Of course, that program became SCORE. They took what SCI learned and asked additional questions about how best to conduct the preventive chemotherapy by MDA, and explore what tools were needed to do it better. Now that SCORE has fulfilled its mission, they are passing their findings and lessons learned, along with recommendations, to other groups. One of these, the recently established Global Schistosomiasis Alliance, which includes some of the same people involved with SCORE, has taken up the baton to help harmonize the continued fight to end schistosomiasis.