Parasitic helminths such as schistosomes and filarial and soil-transmitted nematodes are estimated to infect at least a billion people worldwide, with huge impacts on human health and economic development. In the absence of vaccines, treatment and control of these neglected tropical diseases relies in large part on a small set of anthelmintic drugs. However, diagnosis and monitoring of disease transmission and efficacy of treatment depends almost entirely on methods that are inaccurate, labor-intensive, and unreliable. These limitations are amplified and take on added significance in mass drug administration programs, where measures of effectiveness depend on the ability to accurately monitor treatment success (or failure), changes in disease transmission rates, and emergence of drug resistance. Molecular methods for detection and quantitation of parasite nucleic acids in host fluids or tissues offer reliability, sensitivity, and specificity, but depend on availability f necessary infrastructure, highly-trained staff, and expensive and delicate equipment. The long-term goal of this exploratory project is to overcome these limitations. To do so, we will adapt isothermal molecular assays such as loop-mediated isothermal amplification (LAMP) to a simple, hand-held, point-of-care microfluidic device that allows sensitive and specific detection of helminth parasite nucleic acids in infected hosts. We will use animal models of parasitic helminth infection to demonstrate the feasibility of this technology and as proof of principle. Use of such a device could provide critical advancements in diagnostics, monitoring of disease prevalence and treatment efficacy in mass drug administration programs, and detection of treatment failures that might warrant attention as signs of emerging drug resistance.
The specific aims are to: 1) Optimize isothermal amplification assays of helminth nucleic acids in samples from parasite-infected hosts~ and 2) Develop and demonstrate the feasibility of a simple nucleic acid amplification test for parasitic helminths in a point-of-care device format. Translation of this type of simple, inexpensive, self-contained technology for detection of parasitic helminth nucleic acids in hosts or in the environment could ultimately transform analysis of treatment and control options in the developing world.

Public Health Relevance

Highly prevalent neglected tropical diseases such as schistosomiasis and filariasis have devastating effects on human health and economic development. Current diagnostic methods for these parasitic helminthes infections are often crude, unreliable, and labor-intensive~ newer, more sensitive molecular approaches are expensive and require infrastructure and equipment not readily available in the field. This exploratory project will adapt molecular detection of these parasitic infections to a simple, self-contained, inexpensive chip if successful, this work could lead to groundbreaking changes in diagnosis and monitoring of these neglected tropical diseases.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Pathogenic Eukaryotes Study Section (PTHE)
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Deye, Gregory A
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University of Pennsylvania
Schools of Veterinary Medicine
United States
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Song, Jinzhao; Liu, Changchun; Mauk, Michael G et al. (2017) Two-Stage Isothermal Enzymatic Amplification for Concurrent Multiplex Molecular Detection. Clin Chem 63:714-722
Song, Jinzhao; Mauk, Michael G; Hackett, Brent A et al. (2016) Instrument-Free Point-of-Care Molecular Detection of Zika Virus. Anal Chem 88:7289-94
Liu, Changchun; Liao, Shih-Chuan; Song, Jinzhao et al. (2016) A high-efficiency superhydrophobic plasma separator. Lab Chip 16:553-60
Song, Jinzhao; Liu, Changchun; Bais, Swarna et al. (2015) Molecular Detection of Schistosome Infections with a Disposable Microfluidic Cassette. PLoS Negl Trop Dis 9:e0004318
Greenberg, Robert M (2014) Ion channels and drug transporters as targets for anthelmintics. Curr Clin Microbiol Rep 1:51-60
Greenberg, Robert M (2014) Schistosome ABC multidrug transporters: From pharmacology to physiology. Int J Parasitol Drugs Drug Resist 4:301-9