Notes From the Field

Notes from the field: Enrollment for a year-long prospective study of serum antigenemia in loiasis

In January 2020, two members of the Budge lab, Marla Hertz and Philip Budge, traveled to Cameroon to conduct a field study in partnership with the Center for Research on Filariasis and other Tropical Diseases (CRFilMT). The purpose of the visit was to enroll subjects in a year-long study of loiasis antigenemia. The problem we are working to overcome is that some people with loiasis register as falsely positive in the rapid diagnostic tests (RDT) for lymphatic filariasis (LF). Thus, the test is inconclusive in regions of Central Africa where the two diseases are coendemic. Measures must be taken to improve the specificity of RDTs to facilitate disease mapping and ensure safety during drug treatment.

One problem is that we do not understand why only a subset of people with loiasis are cross-reactive. From our previous work, it appears that cross-reactivity is a transient phenomenon and is associated with the appearance of over 200 L. loa proteins in the blood. Our goal in this study is to follow cross-reactive patients over time to determine if cross-reactivity is transient and to identify factors that predispose or trigger cross-reactivity. We will also analyze loiasis proteins in serum to identify biomarkers that confer false positive RDT results. This study will help us develop more specific diagnostic tools for both LF and loiasis. This work is supported by a Clinical Scientist Development Award granted by the Doris Duke Charitable Foundation

Science Trends Article 2019

https://sciencetrends.com/a-tale-of-two-parasites-how-loiasis-complicates-lymphatic-filariasis-elimination-efforts-in-central-africa/

DDCF Announces the 16 Winners of 2019 Clinical Scientist Development Awards 

Three physician-scientists from Washington University School of Medicine in St. Louis have received a 2019 Clinical Scientist Development Award from the Doris Duke Charitable Foundation. Philip Budge, MD, PhD; Brian DeBosch, MD, PhD; and Andrew Kau, MD, PhD, are among 16 U.S. physician-scientists receiving the awards, which provide $495,000 over three years to each investigator. From left: Philip Budge, MD, PhD; Brian DeBosch, MD, PhD; and Andrew Kau, MD, PhD.

The Clinical Scientist Development Award funds physician-scientists at the early stages of their careers. Faced with the competing demands of both caring for patients and conducting research, physician-scientists often experience a more challenging transition to an independent research career than other researchers. Through this award, early-career physician-scientists are able to protect and dedicate 75 percent of their professional time toward clinical research.

Budge, an assistant professor of medicine, studies lymphatic filariasis, a parasitic worm disease prevalent in tropical regions of Africa and Asia. His research addresses a key obstacle to eliminating lymphatic filariasis in Africa. In severe cases, lymphatic filariasis causes elephantiasis, painfully swollen limbs that make it difficult to walk and carry out daily activities. Programs to eliminate lymphatic filariasis depend on rapid diagnostic tests, but such tests are unreliable in 11 African countries where another worm parasite, Loa loa, is common. That’s because some people with L. loa infection – called loiasis – have antigens in their blood that cross-react with the rapid diagnostic tests for lymphatic filariasis.

Budge is working to determine which L. loa antigens cause cross-reactive tests, why such antigens are present in only a fraction of people with loiasis, and whether these cross-reactive antigens contribute to the adverse reactions that occur when some people with loiasis receive antiparasitic medications.  The results of these studies will help researchers develop improved diagnostic tests for both lymphatic filariasis and loiasis that can help eliminate these neglected tropical diseases.

DeBosch, an assistant professor of pediatrics, studies nonalcoholic fatty liver disease, a condition that affects roughly 25 percent of people in the U.S. and is closely linked to obesity. Intermittent fasting and caloric restriction are effective therapies against the excessive accumulation of fat in the liver. DeBosch’s group discovered that blocking sugar from entering liver cells – the cells that regulate the body’s fasting responses – mimics many of the therapeutic effects of fasting. He is working to generate new therapies that block sugar transport into the liver cells in a “personalized” model of patient-derived liver-like cells.  These personalized liver-like cells will be developed from patients’ urine and used to test novel drugs and genetic treatments.  This modeling will be used as a bridge to identify which subsets of patients stand to benefit the most from each specific therapy.

Kau, an assistant professor of medicine, studies uropathogenic E. coli, the most common cause of urinary tract infections (UTI). They use a specialized adhesin protein called FimH to colonize the urinary tract as well as to establish reservoirs within the gut where they sometimes make their way to the urinary tract to seed infections. Kau will focus on understanding how a promising new investigational FimH-based vaccine, invented by Scott Hultgren, PhD, the Helen L. Stoever Professor of Molecular Microbiology, and subsequently licensed to and developed by Sequoia Sciences, works to prevent infection. His team hypothesizes that this vaccine may work both by preventing E. coli from sticking to the bladder and by selectively reducing uropathogenic E. coli within in the gut. Ultimately, targeting gut reservoirs of pathogens with vaccines like FimH could prove to be an effective approach to prevent drug resistant infections.

“Physician scientists are crucial to the clinical research field because they bring significant insights from their direct interactions with patients from the bedside to the bench,” said Betsy Myers, program director for medical research at the Doris Duke Charitable Foundation. “For this reason, we are proud to support and protect the time devoted to research by these exceptional physician scientists as they balance their clinical obligations with research work, ultimately giving them greater opportunities to make vital contributions to the field.”

Since 1998, the foundation has awarded more than $144 million in Clinical Scientist Development Awards. The Doris Duke Charitable Foundation works to improve the quality of people’s lives through grants supporting the performing arts, environmental conservation, child well-being and medical research, and through preservation of the cultural and environmental legacy of Doris Duke’s properties. The foundation’s Medical Research Program supports clinical research that advances the translation of biomedical discoveries into new preventions, diagnoses and treatments for human diseases.

DOLF Scientists Test New Scanner for Measuring Leg Swelling due to Filariasis

October 19, 2017 Uncategorized

Celia Zhou taking limb volume measurements with the LymphaTech 3D scanner

In March of 2017, DOLF researchers, Ramakrishna Rao and Philip Budge traveled to Galle, Sri Lanka to test a new portable scanner with the potential to revolutionize the measurement of limbs affected by lymphatic filariasis (LF).  The scanner, which is produced by the Atlanta-based startup, LymphaTech, uses infrared scanning technology similar to that found in Microsoft’s X-Box Kinect, to create highly accurate virtual 3D reconstructions of solid objects.  After meeting the scanner’s creators at national meeting in the fall, Doctors Budge and Rao wanted to see if this simple, portable scanner, which consists of an infrared sensor mounted on an iPad, could provide precise and accurate limb measurements for patients afflicted by LF.  So, they worked with Dr. Channa Yahathugoda, who directs a filariasis clinic in Galle, Sri Lanka, to design a study comparing the scanner to the gold-standards for measuring LF-affected limbs: tape measurements and water displacement.

What they found was highly encouraging.  Working together with a team of local physicians in Dr. Yahathugoda’s clinic, they found that the LymphaTech scanner could provide measurements of leg volume and multiple circumferences that were as precise as those obtained by tape measure or water displacement, but in only a fraction of the time, and with much less inconvenience to the patients. This can be a huge step forward for those who study and treat patients with lymphedema, the type of leg swelling caused by LF, because many of these patients have such severe disease that they have difficulty placing their limbs in a water tank to measure water displacement.  In addition, affected legs often have open wound that make it more difficult to take tape measurements.  Many patients often have great difficulty traveling from their homes to the clinic to have their measurements taken.  This new tool should make it possible to take extremely accurate limb measurements in the patients’ homes or villages without cumbersome equipment.  The ability to rapidly get these measurements will make it much easier to monitor patients with lymphedema, particularly in clinical trials of therapies for lymphedema, which are sorely needed.  In fact, after sharing the data from their study with international collaborators, the scanner has been added as a measurement tool in an upcoming multi-site, international research study designed to determine whether the antibiotic, doxycycline, can reduce the severity lymphedema in patients with filariasis.

The Sri Lanka scanner study will soon be published in the American Journal Tropical Medicine and Hygeine.

Read the complete article in Washington University in St. Louis – The Record

A collaborator using the LymphaTech scanner to scan the legs of a patient in Galle, Sri Lanka

One example of the 3D model created by the LymphaTech scanner