Twahirwa Merab of PIVOT ACCESS Ltd. in Rwanda will improve access to credit for poor individuals in Rwanda by developing a credit scoring system so that digital financial service providers can better estimate risk. Their system will integrate data from a range of financial transactions such as utility bill payments and mobile phone top-up frequencies to produce a formal credit history for each individual. They will perform a pilot test involving a Rwandan mobile network operator and bank to assess the feasibility of their system and use the results to refine it.

Daniel Kamei of the University of California Los Angeles in the U.S. will develop a paper-based diagnostic that can rapidly concentrate and detect low concentrations of cervical cancer-specific biomarkers in self-collected vaginal swabs. Cervical cancer is a major health problem, particularly in regions with limited health care where there are no effective screening programs. The test will be evaluated on existing cervical samples that have already been analyzed for HPV and cancer using conventional methods.

Bryan Hsu from Harvard Medical School in the U.S. will develop a mouse model carrying specific bacteria to mimic conditions in the infant gut for studying bacteria-infecting viruses known as phage, which could be valuable agents for treating infectious diseases and promoting child health in developing countries. Understanding how phage behave within the complex human gut is a critical step towards developing phage-based therapeutics that can safely modify resident bacterial populations. They will create a computational model to predict the effects of selected combinations of phage on bacteria dynamics in the mice, and then evaluate a phage-based therapeutic for treating a pathogenic Escherichia coli infection.

Daniel Chiu from the University of Washington in the U.S. will develop a simple assay for use in low-resource settings to determine HIV load, which is critical for optimally treating patients. HIV load is determined by amplifying the RNA of the virus using a polymerase chain reaction (PCR). Current assays use enzymes that require cycles of precise temperatures and thus expensive equipment. They have developed a low-cost and simple digital PCR method on a chip that they will combine with loop-mediated amplification, which uses an enzyme that can amplify RNA at a constant temperature, to quantify HIV viral load. Their assay does not need complicated blood sample preparation or expensive equipment, and the results can be interpreted using a smartphone. They will evaluate it for accuracy, sensitivity and reproducibility compared to standard assays.

Steven Patterson of Imperial College in London will develop a new vaccine strategy that exploits the property of a protein, retinaldehyde dehydrogenase (RALDH), that stimulates immune cells to travel to the gut mucosa and there provide localized immune protection against inhabiting pathogens such as HIV. Using vaccines to generate immune responses specifically at mucosal surfaces such as in the gut or lungs, which are major sites of pathogen entry, is challenging, particularly when the vaccine must be administered with a needle, which delivers it to non-mucosal sites. They will engineer adenoviral vectors to transfer the RALDH gene to dendritic cells, and test whether these cells can then produce the relevant molecules that stimulate T and B cells to home to the gut.

Jennifer Mahony and Douwe van Sinderen of University College Cork in Ireland, with Marco Ventura of University of Parma in Italy, will study how bacteriophage, which are viruses that infect and kill bacteria, affect both beneficial and pathogenic bacterial populations over time in the guts of infants from developing countries, which ultimately influence infant health and well-being. They will take fecal samples at 1, 2, 3 and 6-month time points from healthy children and those with gut disorders in Malawi, Sudan, Ethiopia or Nigeria, and identify the types and levels of bacteria and phage present by sequencing their DNA. These data will be combined with obtained dietary information to identify links between phage populations and the changes in bacterial populations in the gut. They are particularly interested in whether changes in the levels of beneficial bacteria caused by phage might make the gut more vulnerable to colonization by pathogenic bacteria such as enterotoxigenic E. coli (ETEC) and Shigella, which are a major cause of mortality in infants. In parallel, they will identify phage that can kill these pathogenic bacteria and may be developed into new treatments.

Kirill Alexandrov of the University of Queensland in Australia will develop a low-cost diagnostic that uses well-established glucose biosensors to detect DNA of infectious pathogens. The biosensor will be built by splitting the enzyme glucose dehydrogenase in half, and attaching each half to a protein that is engineered by zinc-finger nuclease technology to bind a specific sequence of DNA in a pathogen. In the presence of that pathogen, the enzyme becomes whole and reacts with glucose to produce an electric current that can be read by portable electronic devices including smartphones. They will optimize their approach, tailor it to detect the dengue virus, and evaluate it using bodily fluids such as serum and saliva. They will also test whether they can combine their approach with a simple DNA amplification method to increase the sensitivity of detection.

Reza Nokhbeh from the Advanced Medical Research Institute of Canada in Canada will genetically engineer phage that infect pathogenic Escherichia coli bacteria to express proteins and short RNA molecules that block multiple bacterial functions and thereby stop it from colonizing the human gut and causing disease. Diarrheal diseases cause substantial mortality in children under five in developing countries, and there is an urgent need for new treatments. They will develop their approach to first target E. coli O157:H7 by incorporating genes and RNAs into the phage that promote bacterial cell death, slow growth, and block its ability to produce toxins and attach to host cells. The resultant phage will be tested in a mouse model of the infection.

Aaron Wheeler from the University of Toronto in Canada will develop a cost-effective, portable test that uses microfluidics to rapidly diagnose malaria from saliva samples. The digital microfluidic device is comprised of an array of electrodes over which droplets of samples and reagents can be moved around using a simple operating system. This allows the concentration of samples to enhance the specificity of the test, and the automation of an enzyme-linked immunosorbant assay to detect the presence of malaria antigens, along with a digital readout. They will develop protocols for the assay and for concentrating the samples, and perform a pilot test to evaluate the device for detecting malaria from plasma and oral samples taken from patients in Mozambique compared to conventional methods.

Diane Joseph-McCarthy of EnBiotix Inc. in the U.S. will use a systems biology approach incorporating gene, protein and metabolic data to computationally model the complex interplay between specific microbes in the gut and the host response, and the effect of phage, to enhance our understanding of pathogenic diseases and identify new treatments. They will use a mouse model of enteropathogenic E. coli infection and measure the effect of treatment with phage on the genetic or molecular response of both the host and the resident bacterial populations, as well as the interactions between the two. These data will be incorporated with other publicly available data and modeling algorithms used to produce a visual interaction network that can generate hypotheses for experimental testing.

Travis Lybbert of the University of California, Davis, in the U.S. will develop a simple, low-cost approach that uses mobile phone records to track changes in living standards and use it to evaluate new mobile money saving products and services in Haiti. They will develop prediction algorithms for mobile phone records using in-person and phone surveys collected as part of a planned randomized control trial (RCT), which will be used to evaluate a new type of savings account they are developing with a leading mobile services provider. The adaptive randomized control trial will involve 13,500 working poor in Haiti and will use their mobile phone records to measure the value of the savings account.

Stephen Rogerson from the University of Melbourne in Australia will develop a low-cost diagnostic using an electrical immunosensor platform that can detect very low levels of the malaria parasite in blood and saliva samples to aid malaria-elimination efforts. The platform detects changes in electrical impedance caused by the binding of two molecules, and they postulate that it can improve the limit of detection of current related diagnostic tests by up to 1000 fold. They will develop planar dielectric immunosensors for the malaria-causing Plasmodium parasite by coating the sensors with molecules that bind two specific parasite proteins. The sensitivity and specificity of the sensors will be evaluated using infected blood and saliva samples.

Todd Parsley of SynPhaGen, LLC in the U.S. will engineer phage-like particles to transfer genes into specific bacteria in the infant gut that program them to produce therapeutic proteins that protect against environmental enteric dysfunction, which is a major cause of morbidity and mortality in developing countries. Rather than employing bacteria-infecting phage to destroy bacteria, they will engineer safer particles, which are unable to replicate and do not kill the bacterial host. As proof-of-principle, they will modify the defective bacteriophage particles to carry a gene encoding the protein alkaline phosphatase, which keeps the gut healthy in multiple ways including neutralizing bacterial toxins, and program them to infect the bacterium Bacteriodes thetaiotaomicron. The activity of these particles will then be assessed in a mouse model of environmental enteric dysfunction.

David Low from the University of California, Santa Barbara in the U.S. will engineer phage to selectively target and destroy several pathogenic bacteria to prevent enteric diseases in infants. Lytic phage infect bacteria and hold great promise as therapeutics for infectious diseases, but controlling their activity and preventing the development of bacterial resistance is challenging. They will engineer different versions of the T2 lytic bacteriophage that bind multiple different regions of the BamA protein found on the surface of several pathogenic bacteria, which will ensure they only infect these target bacteria. And, as the BamA protein is essential for bacteria survival, it is unlikely that it will be mutated to cause resistance. They will test the different phage for capacity to kill pathogenic E. coli and Shigella, and whether they cause resistance.

Timothy Julian of the Swiss Federal Institute of Aquatic Science and Technology (EAWAG) in Switzerland will develop a low-cost approach to monitor the development of resistance to antibiotics, which is a major public health concern. Identifying antibiotic resistance requires sequencing and with current protocols is costly. To address this, they will first enrich samples for 30 antibiotic resistance genes using oligo-coated magnetic beads to increase the efficiency of the sequencing and substantially reduce the cost per sample. They will optimize the gene enrichment step by testing different oligos and protocols.

Martha Clokie from the University of Leicester in the United Kingdom will develop a bacteriophage to destroy the diarrhea-causing bacterium Shigella, and study its effect on microbial populations in the gut. Shigella is a leading cause of death in children under five years old in the developing world but there are no effective vaccines due in part to the many different forms of the bacterium. Phage are viruses that can destroy specific bacteria, and are an alternative approach to vaccines. They will perform a longitudinal study in a mouse model of chronic Shigella infection using their collection of 46 lytic phage isolated from infants in Bangladesh that infect 200 clinical strains of Shigella. The effects of the phage will be evaluated both by sequencing to determine the quantities and types of bacteria in the gut, and by analyzing protein production in the bacteria and the mice, which will also reveal insight into the host immune response.

Srivatsan Raman of the University of Wisconsin-Madison in the U.S. will develop a platform for engineering synthetic phage – bacteria-infecting viruses – that can be easily reprogrammed to target specific bacterial species and that can be switched off to improve their safety for treating enteropathogenic diseases in newborns. Natural, so-called lytic phage have two main limitations when being considered as potential therapies: they cause death to bacteria by physically destroying them, which can release large concentrations of lethal toxins into the body, and the bacteria also evolve resistance to the phage, necessitating the identification of new phage, which is a lengthy process. They will focus on producing phage targeting enterotoxigenic Escherichia coli (ST-ETEC), which is one of the most common diarrhea-causing pathogens in infants in developing countries. They will use the Rosetta software to design thousands of proteins and test them for binding to specific bacterial receptors when incorporated into the T7 phage. They will also redesign a protein required for phage replication to make it unstable in the absence of a small molecule so it can act as an on-off safety switch in case of high toxin levels.

Jacqueline Linnes of Purdue University in the U.S. will develop a paper-based diagnostic test that can detect HIV from a pinprick of blood for use in low-resource settings. They will optimize sample preparation by using a series of filters that isolate the virus from blood. They will then test whether wax can be used for heat-controllable valves to move fluid through a paper network to extract the viral RNA, perform an isothermal amplification reaction, and enable visual detection. Reagents for the reactions will be printed onto a paper matrix and optimized for detecting low levels of virus. The printed paper platform is low cost and can be easily scaled-up for manufacturing.

Christopher Mason of Weill Medical College of Cornell University in the U.S. will generate a global map of antimicrobial resistance by using biochemical and computational methods on available samples taken monthly over one year from 24 developed and developing cities across six continents. Each city will be sampled from both high-density (e.g. train stations) and low-density (e.g. parks) areas. They will sequence DNA isolated from two samples per area from each city to identify the bacterial species present and determine whether they carry any antimicrobial resistance genes or markers, or chemically modified DNA bases (epigenetic modifications) that may influence microbial function. The results will then be geographically mapped, and analyzed for associations with population density and proximity to health centers.

Paul Bollyky from Stanford Medical School in the U.S. will study whether filamentous phage – viruses that infect bacteria – direct structural changes in the lining of the intestines and thereby promote the growth of healthy bacteria to protect against disease. Phage are considered to be a potentially rich therapeutic resource for infectious diarrhea and environmental enteropathy, which are prevalent in developing countries, but much remains to be learned about them. They have shown that a phage of the genus inovirus directed the formation of bacterial biofilms, which have specific crystal-like properties. They will use their newly developed software package along with polarization microscopy to image intestinal bacterial populations and analyze the structure of biofilms in human specimens and mouse models, and study the effect of phage, bacterial infection, and diet. They will also measure inovirus from around 2000 stool samples from children in Bangladesh to determine whether the levels decrease in line with the severity of diarrhea, suggesting that this phage might be protective. The effect of these isolated phage on intestinal structure will also be analyzed in mouse models.

Denise Evans from the Wits Health Consortium (Pty) Ltd. in South Africa in collaboration with Peter Rockers from Boston University will evaluate the impact and sustainability of a combined health care package for families offered by community health workers in the home to improve child health in South Africa. The package includes methods that are known to be effective on their own but have never been evaluated in combination including cognitive behavioral therapy for maternal depression and teaching parents new ways to engage and stimulate their children to boost their cognitive and emotional development. They will integrate the package into the current community health worker program for ease of delivery direct to people’s homes, and evaluate it using a pilot cluster-randomized trial involving 2000 households and 100 community health workers.

A reliable, low-cost screening tool to identify high-risk cephalopelvic disproportion (CPD) patients is of paramount importance especially in resource-limited areas where a timely referral to a medical facility for assisted delivery or cesarean section would make the difference between saving the life of mother and child and potential loss of both patients. To address this pressing need we propose to develop and test a simple, ultra-low cost portable technology using off-the-shelf Microsoft Kinect sensor to quantify an obstructive score to identify women at high risk for CPD. The technology will create very high precision 3D patient models from which a plethora of traditional and novel anthropometric and volume measures can be extracted and used in conjunction with machine learning algorithms to establish a clinical score identifying high risk for CPD. This novel technology has the potential to establish a better risk assessment for obstruction than currently available clinical practice in low-resource setting, thus providing a low-cost avenue to save lives at birth.

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.