Neglected Tropical Diseases

Mostafa Zamanian of Iowa State University in the U.S. will take schistosomes, which are parasitic worms that cause a range of infectious diseases, make them sterile, and genetically modify them to deliver anti-parasitic (anthelmintic) agents into humans to protect them against subsequent infections. They will use genome editing, guided by RNA in the worms, to disrupt individual genes required for laying eggs in order to make the worms sterile and thereby non-pathogenic.

James Tibenderana and colleagues of the Malaria Consortium in the United Kingdom are adapting a "community dialogue" approach to build trust between communities and the health system in Mozambique in order to boost participation in Mass Drug Administration (MDA) programs against neglected tropical diseases. Low participation in MDA programs is thought to be caused by negative local perceptions of these diseases and a limited understanding of the goals of MDAs.

Cecilia Bouzat of the Instituto de Investigaciones Bioquímicas de Bahía Blanca in Argentina will develop a drug screening platform to identify new antiparasitic drugs using the model nematode Caenorhabditis elegans. There are limited numbers of effective anthelmintic drugs and resistance to these drugs is emerging in the field. However, parasitic nematodes are unsuitable for large-scale drug screens mainly because they generally require host animals to survive. She will use the related free-living C.

Coenraad Adema of the University of New Mexico in the U.S. will develop a device to attract, capture, and display a signal from the parasitic flatworm Schistosoma mansoni in order to determine transmission risks and support control efforts. Adema will confirm the reported attraction of the parasite larvae to particular chemicals (chemoattractants) and then analyze whether the subsequent release of parasite enzymes can induce a color change that can be quantitatively detected using a chromogenic substrate.

Edward Mitre and colleagues at the Henry M. Jackson Foundation for the Advancement of Military Medicine in the U.S. will develop a short course therapy for clearing adult filarial worms, which cause substantial morbidity and mortality, to enhance eradication efforts. Current antifilarial medications target only larval forms of the worms, requiring repeated administration until the natural death of the adults. Filarial infections are known to induce immune cells to release histamine, which can regulate the immune response.

Eric Loker of the University of New Mexico in the U.S., along with colleagues from KEMRI in Kenya, will test whether parasitic flatworms known as amphistome flukes can eradicate the human parasite Schistosoma with the goal of helping prevent human infections. These two types of worms co-inhabit the same snail species. The investigators will harvest large quantities of amphistome eggs from the rumens of routinely slaughtered goats and cattle, and use temperature and light to induce miracidia (larva) to hatch in the laboratory.

Judy Sakanari of the University of California, San Francisco, and Manu Prakash from Stanford University in the U.S. will develop a cheap electromagnetic detection device to non-invasively assess the viability of parasitic nematode worms in infected patients to guide treatment duration. Current methods of detecting viable worms in nodules or the lymphatic system are invasive or expensive.

Timothy Geary at McGill University in Canada proposed screening chemicals derived from the biological diversity found in Africa to identify lead compounds for the development of drugs to treat infections caused by parasitic nematode worms. In this project's Phase I research, Dr. Geary established drug discovery centers at the Universities of Botswana and Cape Town, South Africa to screen for compounds that target a nematode family of peptidergic G Protein-coupled receptors. In Phase II, the team is expanding the screening efforts.

Timothy Geary at McGill University in Canada proposed screening chemicals derived from the biological diversity found in Africa to identify lead compounds for the development of drugs to treat infections caused by parasitic nematode worms. In this project's Phase I research, Dr. Geary established drug discovery centers at the Universities of Botswana and Cape Town, South Africa to screen for compounds that target a nematode family of peptidergic G Protein-coupled receptors. In Phase II, the team is expanding the screening efforts.

Vishwas Joshi and colleagues from Seagull BioSolutions in India will develop a vaccine against the dengue virus by engineering a defective version of the measles virus to express dengue virus proteins (a so-called virosome), which can induce protective immunity. There is currently no approved vaccine that protects against dengue infection, which causes disease in 50-100 million people annually, some of which are life threatening. They will test the efficacy of the virosomes to prevent dengue virus infection by using them to vaccinate mice and analyzing immunity upon viral exposure.