Awards

Dawn Wesson and Sam Jameson of Tulane University in the U.S. will develop an artificial meal for mosquitoes based on algae as a protein source that can be freeze dried and stored in blister packs, and refine their reusable feeding system. Mosquitoes are currently laboratory reared using expensive and difficult to obtain mammalian blood to ensure adequate numbers of offspring for studying. They proposed that a spirulina (Arthrospira platensis) would be an ideal candidate for feeding mosquitoes due to it being a complex protein source, easy to mass produce, and dark in color, which is a feeding cue for mosquitoes. They will supplement it with insect juvenile hormone, which stimulates egg production, sugar and salt, and test its palatability and effect on egg production in a number of different mosquito species using iterations of their meal delivery system compared to human blood.

Mark Ansermino of The University of British Columbia in Canada will adapt near-infrared spectroscopy (NIRS) for the simple diagnosis and monitoring of children at increased risk of mortality from pneumonia. Children with moderate to severe malnutrition who develop pneumonia are far more likely to die than more nourished children, but diagnosing pneumonia in these individuals is problematic, likely due in part to muscle wasting that masks the classic symptoms of fast breathing and chest indrawing. NIRS is non-invasive and portable, and can rapidly measure tissue oxygenation levels, which will be reduced by oxidative stress in children with malnutrition. They will collect arm muscle saturation data using NIRS on 200 children under five years old admitted for lung infections at a clinic in Uganda, and use the data to design a prototype device and protocols for identifying at risk children.

Flaminia Catteruccia of President and Fellows of Harvard College in the U.S. will produce fabrics and nets treated with the dibenzoylhydrazine (DBH) compound methoxyfenozide, which is toxic to malaria-transmitting mosquitoes, to prevent these insects from entering households and spreading disease. The compound is non-toxic to mammals but disrupts steroid signaling pathways in the mosquito, which is a different mechanism than existing insecticides, reducing lifespan and causing sterility. They will combine it with insecticide and evaluate different formulations on geographically diverse mosquito species in the laboratory. The best formulations will then be tested on specific field-collected outdoor mosquito populations from southern Africa.

Alessio Fasano of Massachusetts General Hospital in the U.S. will isolate bacteriophage (viruses that infect bacteria) that specifically kill pathogenic Escherichia coli and Shigella bacteria, which cause environmental enteropathy and other potentially deadly childhood diseases. They will perform a high-throughput screen using a diverse phage library to isolate phage that specifically target the type-III secretion system expressed by enteric pathogens like E. coli. They will also test an alternative approach by constructing phage to carry so-called CRISPR-Cas9 nucleases that they will engineer to target and cleave bacterial type-III secretion system genes. Results from both approaches will be tested for their capacity to selectively kill enteric pathogens and inhibit infection in a human organoid model, which consists of different cell layers to mimic the structure and function of the human gut.

Joe Gallagher together with Chris Watson of University College Dublin in Ireland will develop a method to quickly and accurately diagnose bacterial pneumonia in children with acute respiratory infections so that the correct treatments can be given. Physical symptoms of bacterial pneumonia are similar to many other diseases including malaria but they require vastly different treatments. They will use a screening approach to identify protein, metabolite or miRNA biomarkers of bacterial pneumonia in blood and urine samples from 500 children in Malawi clinics with a known diagnosis of pneumonia. The most specific biomarker panel will be combined with a selected panel of symptoms such as heart and breathing rate to generate a highly sensitive clinical prediction model that specifically diagnoses bacterial pneumonia and can be used in low- to middle-income countries.

Heba Khamis of the University of New South Wales in Australia will use smartphone technology to more accurately measure malnutrition in children from developing countries, which puts them at increased risk of death from diseases such as pneumonia. They will develop an image-processing algorithm for calculating three key growth parameters (height, and arm and head circumference) and thereby assessing nutritional status from a photograph of a child taken by a smartphone. They will recruit twenty children to help refine the algorithm and the protocol for taking the photograph, which will then be validated on an independent set of children.

Anika Kinkhabwala of EpiBiome in the U.S. will exploit the development of resistance to bacteriophage by pathogenic bacteria to improve children's gut health. Bacteriophage recognize proteins and other molecules found on the surface of bacteria, which they use to infect and kill them. They will identify bacteriophage isolated from fecal and sewage samples that can target virulence structures on the surface of the pathogenic bacteria enterotoxigenic Escherichia coli (ETEC) and Shigella dysenteriae, which are common diarrhea-causing bacteria. Faced with such bacteriophage, pathogenic bacterial populations would become enriched with mutants that escaped phage infection by virtue of having lost these virulence factors, with resistant bacteria thereby less harmful to humans. They will characterize how these bacteria develop resistance to specific phage and build a cocktail of phage that target different bacterial virulence structures to further weaken pathogenic bacteria and help cure diarrheal disease.

Haiqing Sheng and collaborators Carolyn Bohach and Scott Minnich from the University of Idaho in the U.S. will exploit the CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) system in a dual approach to combat enteropathogenic Escherichia coli (EPEC) infections. EPEC cause diarrhea and result in several hundred thousand infant deaths annually. They will engineer a CRISPR-Cas9 cassette to recognize and cleave a DNA sequence found specifically in EPEC, which will lead to selective EPEC cell death in the intestinal tract without affecting other beneficial bacteria. The engineered CRISPR-Cas9 will be administered using both safe EPEC-targeting viruses (bacteriophage) to treat primary infections as well as probiotic E.coli to stably establish the EPEC-targeting plasmid in the gut and block re-infection. They will test it using an established rabbit model of EPEC infection, which will pave the way for future clinical testing.

Brandyce St. Laurent of the National Institutes of Health in the U.S. will test whether cow-baited tents can be used to monitor and control disease-causing mosquitoes in the Greater Mekong Subregion. Most Anopheles mosquitoes preferentially bite animals, but they still contribute to malaria transmission in humans, and many bite outdoors, rendering bednets and indoor repellants useless against them. They will produce low-cost tents treated with insecticide, and locally rent cows as bait. The tents will be set up in both villages and forests and the captured mosquitoes will be analyzed to evaluate the efficacy of their approach.

Rinti Banerjee of IIT Bombay in India will develop skin patches for safer and more effective dosing of the antibiotic amoxicillin in children with pneumonia in developing countries. Amoxicillin is usually provided as a tablet or powder that requires multiple doses per day, which, along with the bitter taste, is off-putting for children. They will develop amoxicillin-enclosed lipid nanoparticles that mimic the outer surface of the skin, and optimize their size and ability to encapsulate the drug. These nanoparticles will be added to multilayered transdermal patches that allow the continued release of amoxicillin through the skin, and contain a dye that indicates when the patch needs changing. The patches will be first evaluated on pigs' skin, and in mice and rats.