Neglected Tropical Diseases

Paul Dyson of Swansea University in the United Kingdom will work to control the incidence of sleeping sickness in humans, which is caused by the Trypanosome parasite transmitted by tsetse flies, by genetically modifying a fly gut bacterium to deliver double-stranded (ds) RNAs to block two important parasite proteins. Trypanosomes mature in the flies, thereby gaining the capacity to infect mammals. He will engineer the bacteria and introduce them into tsetse flies, then test the capacity of the dsRNAs to inhibit their target proteins in trypanosomes.

Andrew Jackson of the University of Liverpool in the United Kingdom will develop a diagnostic tool for Animal African Trypanosomiasis (Nagana), which is caused by unicellular parasites known as trypanosomes and threatens up to 50 million cattle in sub-Saharan countries. To avoid immune detection, the causative trypanosomes change their DNA sequences (genomes), particularly in genes encoding for cell surface glycoproteins, which also affects the symptoms the parasites cause.

Floriano Silva of Fiocruz in Brazil will develop a drug screening assay using automated microscopy to test new drug candidates for toxicity towards adult helminth parasites, which cause a range of diseases. Current screening approaches cannot easily identify drugs that specifically target adult parasites, which is the most disease-relevant life cycle stage. He will develop and validate imaging and computational methods to automatically monitor physical characteristics of the parasites, and perform proof-of-principle drug screens using an FDA approved and an annotated compound library.

L. David Sibley at Washington University in St. Louis in the U.S. is developing a long-term in vitro intestinal epithelial culture system for the intracellular parasite Cryptosporidium, which causes severe diarrheal disease in both humans and animals, and is refractory to many anti-parasitic drugs. Currently, Cryptosporidium can only be grown in infected calves or in short-term in vitro cultures, which cannot be used for the high-throughput chemical screens needed to identify new drugs.

Nils Pilotte and Steven Williams of Smith College in the U.S. along with Lisa Reimer at the Liverpool School of Tropical Medicine in the United Kingdom are developing a simple and inexpensive approach to monitor diseases caused by parasites that thrive in mosquitos based on detection in mosquito feces. Current approaches for disease surveillance are expensive, insensitive, or labor intensive, and are generally unsuitable for the areas in which they are needed most, including where disease incidence has decreased.

Sanjiban Banerjee and Sambuddha Ghosh at AbGenics LifeSciences Pvt. Ltd in India will develop a new method to treat intestinal worm (helminth) infections using modified probiotic strains of the bacterium Lactobacillus. Lactobacillus, which can live in the human gut, will be modified to produce stable RNA molecules selected to target specific helminth genes and ultimately destroy the parasite, thereby curing the infection. Because Lactobacillus colonizes the gut, it can be used as a long-term treatment for multiple helminth infections.

Danae Schulz and Erik Debler of Rockefeller University in the U.S. will test whether a drug that was originally developed to treat cancer and heart disease can also kill trypanosomes, which are parasites that cause African trypanosomiasis in humans and cattle. Repurposing a drug already approved for a different disease is highly cost-effective as expensive human safety trials are already complete. This particular drug is a bromodomain inhibitor that interferes with the structure of chromatin, and they have shown that it destroys trypanosomes grown in vitro.

Mbutolwe Mwakitalu of the National Institute for Medical Research in the United Republic of Tanzania will expand treatment of parasitic worm infections to nomads in Tanzania by coupling the provision of anthelmintic drugs with drugs and vaccines for livestock, which are highly valued by this community. Mass drug administration campaigns have had limited success on nomadic communities because of their motility and relatively low interest in personal health compared to the health of their livestock.

Stephanie Richard of Health & Development International in the U.S. will run a campaign in Togo to identify and treat individuals with severe chronic morbidities caused by infectious diseases. Although several neglected tropical diseases such as lymphatic filariasis have been well controlled by mass drug administration efforts in Togo, they cause many lasting and severe secondary effects that require expensive treatments such as surgery, and are therefore not widely available.

Brian Foy of Colorado State University in the U.S. will test whether repeated administration of the anti-parasitic drug ivermectin specifically during the short dry-to- rainy transition in Burkina Faso in combination with distribution of insecticide treated nets will better reduce the incidence of malaria, lymphatic filariasis and soil transmitted helminth infections. Incidence of these diseases remains high despite mass drug administration efforts.