Neglected Tropical Diseases

Fidelis Cho-Ngwa of the University of Buea in Cameroon will develop a small animal model to test the safety of candidate drugs for treating the parasitic disease onchocerciasis in people who are coinfected with the Loa loa parasite. Ivermectin, which is used in mass drug administration efforts to treat onchocerciasis, causes severe adverse effects, including death, in people who carry high levels of Loa loa.

Tim Day and Mostafa Zamanian of Iowa State University in the U.S. will evaluate a new approach for treating parasitic worm infections based on blocking parasite microRNAs. Parasitic worms (helminths), such as Schistosoma, release small vesicles called exosomes containing microRNAs, which are thought to target host genes and aid infectivity. They will test this directly using a mouse model of schistosome infection by identifying the relevant microRNAs, designing anti-microRNAs to block them, and determining if the mice can be made resistant to infection.

Eileen Devaney and Elmarie Myburgh of the University of Glasgow in the United Kingdom will determine whether parasitic filarial worms can be visualized in the lymphatic system of live animals as a means to measure drug activity. Testing candidate anti-filarial drugs using in vivo models is preferable to the current in vitro assays because the selected drugs are more likely to be effective in humans. They will infect mice with either larval or adult stage parasites, and then inject them with bioluminescent substrates of specific immune cells.

Louise Kelly-Hope of the Liverpool School of Tropical Medicine in the United Kingdom and Thomas Unnasch of the University of South Florida in the U.S., along with their research teams, will develop high resolution tools to map the locations and chart the habitats of vectors of several parasitic worm infections to promote safer and more effective control strategies. Some of the drugs that can successfully treat parasite infections become harmful in the presence of other parasites, but predicting where these co-infections are most likely to occur is difficult.

Kelly Johnston and others from the Liverpool School of Tropical Medicine in the United Kingdom will develop a cell line from a parasitic filarial nematode worm that can proliferate continuously in vitro to enable high-throughput screening of candidate anti-filarial drugs. Current drug screening efforts are limited by the complex life cycle of the worms and the difficulties of obtaining sufficient numbers of worms.

Robert Greenberg of the University of Pennsylvania in the U.S., along with Bernadette Ardelli of Brandon University in Canada, will test whether anthelmintics, which are drugs used to treat diseases caused by parasitic worms, can be improved by combining them with inhibitors of ATP-binding cassette (ABC) multidrug transporters. Of the few anthelmintics available, many are of limited use or become ineffective due to the emergence of drug resistance.

Paula Ribeiro of McGill University in Canada will develop a simple diagnostic test for schistosomiasis, which is caused by parasitic worms, based on microRNAs. Current diagnostics suffer from lack of sensitivity or an inability to distinguish current from past infections. They will evaluate parasite microRNAs contained within small extracellular vesicles (exosomes) as infection biomarkers by first isolating and sequencing them from infected mice.

Yanping Chen of the University of California, Riverside in the U.S. will develop an inexpensive and robust sensor to directly measure the real-time density of insect vectors that transmit parasitic diseases to help plan intervention and treatment programs. Preliminary results indicate that insects can be classified based on the frequency of their wingbeats, which also varies depending on the time of day. Chen will develop an accurate detection system by investigating combining wingbeat frequency with circadian rhythms and other behaviors.

Kaveh Ashrafi of the University of California, San Francisco in the U.S. will use the free-living model nematode worm Caenorhabditis elegans as a molecular platform to identify new drugs capable of killing adult filarial parasitic worms, which cause serious infections. C. elegans is a non-parasitic model organism that can be easily grown and manipulated in the lab, unlike related parasitic Roundworms. Ashrafi will genetically engineer C. elegans to carry the parasitic version of the gene encoding phosphodiesterase-4, inhibition of which is known to kill the parasites.

Tony Goldberg of the University of Wisconsin-Madison in the U.S. will promote the use of flip-flop-style sandals to disrupt the transmission of soil-borne helminths in rural Uganda. Soil-transmitted helminth infections are one of the most common infections worldwide. Their transmission can be disrupted by wearing sandals, but convincing people to wear them has proven challenging.