Awards

Pamela Schnupf of Paris Descartes University in France will develop an oral vaccine to prevent infectious diarrhea in children by engineering a non-pathogenic bacteria to express pathogen molecules that can be safely delivered in bacterial spores. Diarrheal disease caused largely by Shigella and enterotoxigenic Escherichia coli is a major cause of morbidity and mortality in children under five years of age in low-resource settings. Segmented filamentous bacterium (SFB) is non-pathogenic and normally colonizes the human gut during infancy and stimulates the immune system to protect against infections. They will establish methods to genetically engineer SFB to express selected antigens from enterotoxigenic E.coli and test whether it can stimulate an immune response and protect against infection using established mouse models.

Gerard Cangelosi and colleagues at the UW Foundation in the U.S. will develop an oral swabbing method as a lower-cost safe and simple way to diagnose tuberculosis. Tuberculosis is a major global health threat and prompt diagnosis and treatment are critical for reducing spread. Currently a diagnosis is made by testing sputum from deep in the lungs produced by coughing. This can be difficult to collect and produce particularly for children and hazardous for health care workers. They previously found that DNA from the causative Mycobacterium tuberculosis accumulates on oral epithelial cells in infected adults and can be detected by non-invasively swabbing the mouth followed by quantitative PCR analysis. They will improve the sensitivity of this method in adults by testing different swabbing materials and protocols using around 175 suspected tuberculosis-positive patients in a clinic in South Africa. If successful they will test whether their method can also be used to diagnose tuberculosis in children.

Stephen Trowell from the Commonwealth Scientific and Industrial Research Organization in Australia will develop a highly sensitive low-cost and low-invasive diagnostic test for malaria that detects volatile chemicals in exhaled breath. Malaria is one of the most severe infectious diseases affecting hundreds of millions of people per year. Although several diagnostic tests are available they are relatively complex and expensive suffer from limited sensitivity and all require a sample of blood. To overcome these limitations they have developed a test that can detect malaria based on a signature of volatile chemicals (thioethers) released in the breath of patients with so-called controlled human malaria infection. They will now determine whether their signature has diagnostic value also in clinical settings in three distinct genetic and ecological environments namely children at risk of malaria in Malawi and at-risk adults in Bangladesh and in Malaysia by measuring the levels of thioethers in the breath. Finally they will assess the predictive power of their signature for breath diagnosis of malaria in patients in eastern Sudan.

Andrew Prentice of the Medical Research Council in the United Kingdom will conduct a phase II clinical trial to test the ability of a unique nano iron compound to safely and more effectively treat iron-deficiency anemia in children. Iron-deficiency anemia is a common condition particularly in women and children in resource-poor settings and can be deadly. Current iron supplements have limited effects in these settings and undesirable side effects including increasing the risk of infectious diarrhea in children which causes severe morbidity and mortality. They previously developed a compound iron hydroxide adipate tartrate that acts like dietary iron as it can be directly absorbed in humans keeping it away from any resident intestinal pathogens that also use it as a nutrient source. They will perform an intervention study with 600 iron-deficient anemic children in The Gambia and compare their compound with the current supplement to see if it can normalize iron levels without the side effects.

Rakesh Jain of Massachusetts General Hospital in the U.S. will develop a new treatment strategy for tuberculosis to boost the activity of existing anti-tuberculosis drugs. Tuberculosis is one of the most infectious diseases in the world. Current treatments are lengthy poorly tolerated and do not eradicate latent infections which are found in around one third of the general population and contribute to drug resistance. During latent infection the tuberculosis bacteria are dormant and reside in small inflammatory areas in the lungs known as granulomas. These granulomas are surrounded by abnormal blood vessels and dense tissue that they hypothesize make it difficult for drugs to permeate. They will use a small animal disease model and patient lung samples to test whether co-treatment with anti-angiogenics and anti-fibrotics can normalize the blood vessels and improve the delivery of anti-tuberculosis drugs thereby increasing their activity and potentially shortening treatment duration.

Louis Schofield of James Cook University in Australia will develop a broad-spectrum malaria vaccine that is effective against different life-cycle stages of multiple species of the causative Plasmodium parasite. More than one third of the world's population is at risk of contracting malaria. However developing an effective vaccine is challenging because humans are infected by five quite distinct Plasmodium species. In addition the parasites pass through very different developmental stages including sporozoites which mosquitoes inject into the human bloodstream a disease-causing blood stage and a transmissible sexual stage. Using Grand Challenges Explorations funding they have already identified a surface oligosaccharide antigen conserved in several Plasmodium species that when combined with generic carriers and adjuvants can generate a strong immune response that blocks several life-cycle stages in animal models. They will perform further key preclinical evaluations to determine the full efficacy of the vaccine and whether it should proceed to testing in humans.