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Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.

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Online-Offline Collaboration on CDR/Psychometric Microloans

Iris BraunInstitute for Financial Management and ResearchChennai, Tamil Nadu, India
Grand Challenges Explorations
Financial Services Data
1 May 2016

Iris Braun of IFMR LEAD in India will expand access to microloans for the poor in Bangladesh by piloting a simple credit-scoring test for rating individuals. Poor households are often in need of small, short-term loans to buffer fluctuations in income, but formally accessing these loans is problematic as most people have no credit score, and/or are unable to complete the application process. Their approach involves assessing customers by accessing their mobile customer data, such as top-up frequency, and by psychological testing, as well as performing a social survey to analyze local financial needs. The scores can then be passed to mobile money lenders to give them more confidence to lend to poorer households.

From FAST To FIRST and Handy: Rapid Detection of AMR

Tim InglisThe University of Western AustraliaCrawley, Western Australia, Australia
Grand Challenges Explorations
Drug Resistance Burden
1 May 2016

Tim Inglis from the University of Western Australia in Australia will develop a screening test that can be used in remote and low-resource settings to detect antibiotic resistance and ensure the right antibiotics can be prescribed. The emergence of antimicrobial resistance is a huge threat to global public health, and therefore needs to be accurately and rapidly detected, characterized and monitored. They will further develop their method based on flow cytometry that uses fluorescent dyes to rapidly detect changes in bacterial cells upon first exposure to an antibiotic. Different combinations of antibiotics, bacteria and colored dyes will be evaluated, and the test will be analyzed for sensitivity and specificity.

Creating A Micro-Credit Reference Bureau

Twahirwa MerabPivot Access LtdKigali, Rwanda
Grand Challenges Explorations
Financial Services Data
1 May 2016

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.

A RDT Skin Patch for Non-Invasive Malaria Detection

Peter LillehojMichigan State UniversityEast Lansing, Michigan, United States
Grand Challenges Explorations
Global Health Solutions
1 May 2016

Peter Lillehoj of Michigan State University in the U.S. will develop a low-cost skin patch that can rapidly and safely detect malaria. Current diagnostics for malaria generally require the extraction of blood, which is painful and prohibited in certain cultures. The patch will consist of an array of microneedles that painlessly collects interstitial fluid from just beneath the skin surface that is known to contain proteins from the malaria parasite in infected individuals. This sample will then be transferred to a lateral flow test strip that carries a malaria protein-specific antibody. In the presence of malaria, the test strip would indicate a positive diagnosis by displaying colored lines. They will optimize the performance of the patch by testing different arrangements of microneedles and different methods of fabrication, and develop a prototype for preliminary evaluation on synthetic and animal skin samples spiked with malaria.

Thermodynamic Detection of Cancer Biomarkers on Paper

Daniel KameiUniversity of California, Los AngelesLos Angeles, California, United States
Grand Challenges Explorations
Global Health Solutions
1 May 2016

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.

A Cheap and Useful Kit for Malaria Diagnosis in Saliva

Oscar NoyaInstituto de Medicina Tropical, UCVCaracas, Venezuela
Grand Challenges Explorations
Global Health Solutions
1 May 2016

Oscar Noya at the Instituto de Medicina Tropical in Venezuela will develop a simple, low-cost test based on the detection of parasite antigens that can be used to diagnose malaria in low-resource settings. They have developed a multi-antigen blot assay that can diagnose 26 diseases at the same time using saliva or small volumes of blood at low cost without the need for specialized equipment. They will use bioinformatics tools to select synthetic peptides from the malaria-causing parasite Plasmodium falciparum, and from other common pathogens such as HIV and dengue virus. The synthesized peptides will be spotted on cellulose paper and tested for their ability to detect the corresponding disease from sera and saliva samples taken from at-risk populations.

Toward Rational Remodeling of the Infant Gut Microbiota

Bryan HsuHarvard Medical SchoolBoston, Massachusetts, United States
Grand Challenges Explorations
Bacteriophage
1 May 2016

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.

From Clinic to Cloud: Crowdsourcing Resistance Surveillance

William HanageHarvard School of Public HealthBoston, Massachusetts, United States
Grand Challenges Explorations
Drug Resistance Burden
1 May 2016

William Hanage from the Harvard T. H. Chan School of Public Health in the U.S. will develop an approach to better monitor the evolution and spread of microbial resistance to antibiotics, which is a major public health concern. Current approaches are generally slow, not widely available, and limited to analysis of a single pathogen, while often multiple pathogens coexist in each sample. They will trial a method they have developed to identify DNA sequences (motifs) linked with resistance to pneumococcus and gonococcus from existing genomic data. A reference database will be built that stores the identified resistance motifs and Bayesian model of resistance prediction in a cloud. This database can be updated over time. They will also adapt a mobile phone-sized portable DNA sequencer – the Oxford Nanopore minION instrument – for detecting these resistance motifs from human tissue samples such as urine that contain mixtures of DNA, and evaluate its capacity for detecting resistant organisms.

Digital LAMP Point-of-Care Assay for HIV Viral Load Testing

Daniel ChiuUniversity of WashingtonSeattle, Washington, United States
Grand Challenges Explorations
Global Health Solutions
1 May 2016

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.

Novel, Urine-Based Test for Cervical Cancer Screening

Laura MusselwhiteHospital de Câncer de BarretosBarretos, São Paulo, Brazil
Grand Challenges Explorations
Global Health Solutions
1 May 2016

Laura Musselwhite of the Hospital de Câncer de Barretos in Brazil will develop a low-cost test for cervical cancer that women can easily perform at home even in low-resource settings. The test is based on a nitrocellulose strip coated in antibodies to detect the cancer-causing E6 protein produced by the human papillomavirus, which causes cervical cancer. They will enroll 50 women attending their clinic including cervical cancer patients to provide samples for adapting the assay for optimal detection in urine and simplifying it for use in non-clinical settings.

A Parenteral Vaccine to Induce Mucosal T And B Cell Immunity

Steven PattersonImperial College LondonLondon, United Kingdom
Grand Challenges Explorations
Global Health Solutions
1 May 2016

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.

Sniffing Out Malaria: Dogs to Identify People with Malaria

Steve LindsayUniversity of DurhamDurham, United Kingdom
Grand Challenges Explorations
Global Health Solutions
1 May 2016

Steve Lindsay of the University of Durham in the United Kingdom will develop a non-invasive test to block the reemergence of malaria in disease-free regions by training dogs to identify specific odors that are released from people carrying the malaria parasite. It is known that people infected with the malaria-causing parasite Plasmodium falciparum produce thioethers in their breath, possibly to attract mosquitoes so that the parasite can spread more quickly to other people, thereby promoting malaria transmission. Dogs have a highly advanced sense of smell and are used at airports to detect drugs, explosives and fruit. They have also shown potential for helping to detect diseases including cancer. The investigators will take breath and skin samples from 30 asymptomatic but parasite-positive individuals both before and after treatment, and 30 negative individuals. Professional trainers will be used to help evaluate the ability of a dog to detect the difference between the positive and negative samples by training them over a two-month period.

The Role of Phages in Infant Gut Microbiome Modulation

Jennifer MahonyUniversity College CorkCork, Ireland
Grand Challenges Explorations
Bacteriophage
1 May 2016

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.

Vaccination-Passive Transfer to Enhance Germinal Centers

Ian CockburnThe Australian National UniversityActon, Australian Capital Territory, Australia
Grand Challenges Explorations
Global Health Solutions
1 May 2016

Ian Cockburn from the Australian National University in Australia will test two approaches to improve vaccines by increasing competition for the vaccine antigen by immune cells and prolonging the survival of those immune cells. Antibody-producing B cells develop in so-called germinal centers within lymph nodes in response to infections or vaccinations. However, many diseases including malaria lack effective vaccines. They will combine a major vaccine candidate for malaria, Plasmodium falciparum circumsporozoite protein (CSP), with both a monoclonal anti-CSP antibody (so-called passive vaccination), and an immune cell-stimulating molecule hIL-21, both individually and in combination. These will be tested in mice for promoting antibody production and a protective immune response by measuring malaria parasite levels in the liver.

Repurposing Glucose Monitoring Technology for DNA Detection

Kirill AlexandrovUniversity of QueenslandBrisbane, Queensland, Australia
Grand Challenges Explorations
Global Health Solutions
1 May 2016

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.

SMS-Based Commodity and Transport Exchange

Wilson CusackTrade Co.Grand Rapids, Michigan, United States
Grand Challenges Explorations
Financial Services Data
1 May 2016

Wilson Cusack from Trade Co. in the U.S. will develop an SMS-based platform to provide information on market prices and facilitate trade for small-scale farmers in developing countries. The platform will maintain user anonymity, and also handle payments thereby promoting the use of mobile money. It will also enable the arrangement of transportation of goods, and provide a database for monitoring agricultural production and markets. He will further develop the platform for pilot-testing by 100 farmers in Ghana.

Reversal of Virulence of Pathogenic E. Coli

Reza NokhbehAdvanced Medical Research Institute of CanadaSudbury, Ontario, Canada
Grand Challenges Explorations
Bacteriophage
1 May 2016

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.

Portable Toilets as a Health Surveillance Platform

Francisco DiéguezDisalSantiago, Chile
Grand Challenges Explorations
Drug Resistance Burden
1 May 2016

Francisco Diéguez from Disal in Chile will determine whether samples collected from portable toilets found across Pacific coastal regions in South America can be used to monitor pathogenic diseases and antibiotic resistance and help combat these major public health concerns. The portable toilets are tagged with electronic chips that are used to monitor their location and state. They will develop a method for weekly collection and storage of fecal and urine samples from toilets in and around Lima, Peru. Existing methods including immune assays will be used to identify the bacterial species and the presence of antibiotic resistance in the samples, and these will be geographically mapped across communities and correlated with local medical reports.

A Digital Microfluidic Method for Rapid Malaria Diagnostics

Aaron WheelerUniversity of TorontoToronto, Ontario, Canada
Grand Challenges Explorations
Global Health Solutions
1 May 2016

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.

Real-Time Financial Service Location Planning and Search

Tyler RadfordHumanitarian OpenStreetMap TeamWashington, District of Columbia, United States
Grand Challenges Explorations
Financial Services Data
1 May 2016

Tyler Radford from Humanitarian OpenStreetMap Team in the U.S. will partner with the local tech community in Uganda to develop web- and phone-based applications that enable individuals to locate their nearest financial services such as an ATM or mobile money provider, and help financial service providers identify the best locations to expand access across developing countries. They will build a phone-based application for consumers that includes a simple search function as well as the ability to upload relevant information about the financial service, such as opening hours, to increase the value of the application. They will also develop a discovery application incorporating data from the existing OpenStreetMap, which includes locations of existing financial services, schools etc., and can identify underserved areas that would benefit from new services. The applications will be pilot-tested in Uganda, and success measured by the number of users and subsequently by the degree of expansion of financial services.

Integrated Systems Biology for Phage/Microbiome Modeling

Diane Joseph-McCarthyEnBiotixCambridge, Massachusetts, United States
Grand Challenges Explorations
Bacteriophage
1 May 2016

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.

Universal Pathogen Detection in Post Mortem Tissues

Robert SchlabergUniversity of UtahSalt Lake City, Utah, United States
Grand Challenges Explorations
Global Health Solutions
1 May 2016

Robert Schlaberg from the University of Utah in the U.S. will develop an approach that can detect all viruses, bacteria, fungi and parasites in post-mortem samples in order to identify the cause of death and inform disease-control efforts. Determining whether a specific pathogen caused the death of an individual is difficult with current methods partly because of the wide variety of pathogens and the potential for contamination of the tissues. They have developed an analysis tool – Taxonomer – that can identify individual pathogens from sequencing RNA in tissues. They will optimize these methods for post-mortem tissues, which contain fragmented RNA, and test them on known positive post-mortem tissues and fluids. They will also develop an approach that can use post-mortem samples to differentiate between death caused by infectious agents versus non-infectious causes by analyzing samples for specific immune responses that are linked to a range of infections.

Using MPRS to Estimate Outcomes and Enable Adaptive RCTs

Travis LybbertUniversity of California, DavisDavis, California, United States
Grand Challenges Explorations
Financial Services Data
1 May 2016

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.

Phagocins: Precision Tools for Remodeling the Gut Microbiota

Ry YoungTexas A&M AgriLife ResearchCollege Station, Texas, United States
Grand Challenges Explorations
Bacteriophage
1 May 2016

Ry Young III from Texas A&M AgriLife Research in the U.S. will engineer particles that resemble bacteria-infecting viruses (phage), but are functionally defective, for developing treatments that can more safely modify bacteria in the infant gut and thereby protect against disease and malnutrition. So-called lytic phage physically destroy the bacteria they infect and are considered to be potentially highly valuable for treating many childhood infectious diseases that are prevalent in developing countries and cause substantial morbidity and mortality. However, phage can randomly change their behavior by mutating their genome, and can transfer genes between different species, raising safety concerns. They will modify the defective prophage PBSX from the harmless bacterium Bacillus subtilis to produce phage-like particles - phagocins - that cannot replicate and that kill bacterial cells without lysing them. They will evaluate the ability of the phagocins to infect and kill a variety of bacteria, and optimize methods for their low-cost production.

Ultra-Sensitive Non-Invasive Point-of-Care Immunosensor for Malaria

Stephen RogersonUniversity of MelbourneMelbourne, Victoria, Australia
Grand Challenges Explorations
Global Health Solutions
1 May 2016

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.

New Analytics Approaches to Increase Mobile Money Adoption

Amy SmithHuman Network International (HNI)Washington, District of Columbia, United States
Grand Challenges Explorations
Financial Services Data
1 May 2016

Amy Smith of Human Network International in the U.S. will provide free financial services information to mobile phone users in Malawi, and collect data such as mobile call details to help design and deliver better financial services. They have an existing free information service on a range of topics that they will supplement with financial inclusion material so that customers can dial in for free and request information of interest to them. Once the service is launched, they will collect mobile phone data on users and develop analytics approaches that can generate strategies to help mobile network operators acquire new mobile money clients. They will also calculate the overall cost between offering the service for free minus the income generated from creating new clients, which will lead towards promoting the approach in other African countries.

Bacteriophage Particles to Target the Intestinal Microbiome

Todd ParsleySynPhaGen, LLCGaithersburg, Maryland, United States
Grand Challenges Explorations
Bacteriophage
1 May 2016

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.

Photoacoustic Imaging to Quantitate Mycobacterium tuberculosis Burden

Harvey RubinUniversity of PennsylvaniaPhiladelphia, Pennsylvania, United States
Grand Challenges Explorations
Global Health Solutions
1 May 2016

Harvey Rubin from the University of Pennsylvania in the U.S. will develop a new quantitative imaging technology that uses acoustics to measure the total body levels of the tuberculosis-causing bacterium, Mycobacterium tuberculosis. Current imaging methods are generally expensive or unable to measure in all parts of the body. This technology involves shining near-infrared light, which is safe and can penetrate deep into the body, to thermally expand a molecule activated in the presence of M. tuberculosis. This thermal expansion results in the emission of a specific sound that can be detected using standard ultrasound equipment. They have selected a reducing enzyme from the bacterium for activating the molecule, and will build around 100 different combinations of the enzyme substrate, linker and light-absorbing molecule. These will be tested in the laboratory using various models and a high-resolution real time 3D photoacoustic scanner to identify the optimal conjugate.

Strategy for Development of Enteric Pathogen-Specific Phage

David LowUniversity of California Santa BarbaraSanta Barbara, California, United States
Grand Challenges Explorations
Bacteriophage
1 May 2016

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.

Multimodal Satellite Rainfall Measurement for Index Insurance

Ralph LinGroundtruth, LLCWashington, District of Columbia, United States
Grand Challenges Explorations
Financial Services Data
1 May 2016

Ralph Lin and Kathryn Vasilaky of Groundtruth, LLC in the U.S. will develop a new approach to more accurately measure rainfall across farming regions in developing countries so that insurers can make more informed and rapid decisions for paying out to small-scale farmers with insurance against seasonal crop loss. This will also help farmers decide the best time to plant their crops, which is critical for maximizing yield. Satellite data are not currently accurate or stable enough to measure rainfall over small areas. They will further develop their existing low-cost field sensors to automatically upload rainfall data to a cloud server, and develop an SMS-platform that allows farmers to register their own rainfall measurements on the same server. Combining these two methods, along with satellite data, should improve the confidence of the measurements. They will recruit farmers in India to test their approach and help optimize it.

Massive Sample Pooling and Sequencing for Prevalence Rates

Timothy JulianSwiss Federal Institute of Aquatic Science and TechnologyDübendorf, Switzerland
Grand Challenges Explorations
Drug Resistance Burden
1 May 2016

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.

Financial Data Mapping In East Africa

James GouldingUniversity of NottinghamLoughborough, United Kingdom
Grand Challenges Explorations
Financial Services Data
1 May 2016

James Goulding from the University of Nottingham in the United Kingdom will address the knowledge gap in developing countries that is hampering development particularly of financial services by accessing real-time mobile phone call records and mobile financial transactions and using them to locate and model financial behavior across Tanzania. This approach could be faster, lower cost and more reliable than existing approaches that use small sample sizes or are based on crowd-sourcing. They will mathematically process call records to extract location, and produce nation-wide informational maps supplemented by data from unmanned aerial vehicles and local residents for regions lacking detailed maps. These data will then be used to generate predictive models of financial flows, mobility and communications across the country for informing financial service providers and commercial enterprises. Their approach will be evaluated by comparison with existing models.

Developing Bacteriophages to Eradicate Infant Shigella

Martha ClokieUniversity of LeicesterLeicester, United Kingdom
Grand Challenges Explorations
Bacteriophage
1 May 2016

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.

Measurement of Somatic Hypermutation Induced By C3d Adjuvant

Sai ReddyETH ZürichZürich, Switzerland
Grand Challenges Explorations
Global Health Solutions
1 May 2016

Sai Reddy of ETH Zürich in Switzerland will study how low levels of the immune system-stimulating molecule C3d attached to a protein from a pathogen (antigen) can lead to the production of large numbers of pathogen-fighting antibodies and thereby boost the efficacy of vaccines. They hypothesize that it involves stimulating the process of somatic hypermutation in antibody-producing B cells, which results in high titers of antibodies that can bind very strongly to the target pathogen. They will generate the C3d protein fused to a number of different antigens, use them to immunize mice, and subsequently analyze somatic hypermutation using high-throughput sequencing of antibodies and bioinformatics methods.

Editing the Newborn Gut Microbiome Using Engineered Phage

Srivatsan RamanUniversity of WisconsinMadison, Wisconsin, United States
Grand Challenges Explorations
Bacteriophage
1 May 2016

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.

SMS Psychometric Credit Scoring

Julia ReichelsteinEFL Global Ltd.Hamilton, Bermuda
Grand Challenges Explorations
Financial Services Data
1 May 2016

Julia Reichelstein of EFL Global Ltd in Bermuda will promote access to financial services for poor communities by producing a psychometric test for distribution by SMS that can identify dependable new customers and evaluate the risk of lending to them. Individuals in developing countries that would benefit from credit to break out of poverty and in turn boost economic growth are often unable to access financial services largely due to their lack of credit history. They have developed a simple questionnaire that evaluates psychometric traits such as intelligence, business acumen and honesty, to measure risk and future earning potential. They will create an automated SMS version to expand distribution while decreasing costs, and engage with a lending partner for pilot testing in a developing region with a large rural population.

Ultra-Low-Cost Paper-Based Nucleic Acid Diagnostic Platform

Jacqueline LinnesPurdue UniversityWest Lafayette, Indiana, United States
Grand Challenges Explorations
Global Health Solutions
1 May 2016

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.

Bridging Mobile and Financial Data for Agency Banking In DRC

Rupert ScofieldFINCA International, Inc.Washington, District of Columbia, United States
Grand Challenges Explorations
Financial Services Data
1 May 2016

Rupert Scofield from FINCA International, Inc. in the U.S. will promote financial inclusion in the Democratic Republic of Congo by partnering with First Access and mobile network operators to build a credit-scoring model for individuals based on mobile phone usage and financial data. The aim is to provide financial services and develop new products for the unbanked majority.

Global Distribution and Epigenetic Stratification of Antimicrobial Resistance

Christopher MasonWeill Medical College of Cornell UniversityNew York, New York, United States
Grand Challenges Explorations
Drug Resistance Burden
1 May 2016

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.

NIFTY: A Neonatal Intuitive Feeding Technology for preterm infants who have difficulty breastfeeding

Trish CoffeyProgram for Appropriate Technology in Health (PATH)Seattle, Washington, United States
Grand Challenges for Development
Saving Lives at Birth
1 May 2016

The NIFTY cup's extended reservoir off the cup lip optimizes efficient milk delivery, and mothers can directly express into the 60-ml cup. The NIFTY cup's soft silicone material protects the infant's mouth from injury. The cup has embossed volume measurements to track intake; is designed to enhance finger and wrist control over milk flow; and is made with quick-drying, UV- and heat-resistant, durable, affordable silicone that can be boiled for sterilization. Our project aims to 1) generate an evidence base by validating the NIFTY cup in a hospital in Ethiopia and 2) shape the sub-Saharan Africa market by identifying a commercialization partner and developing a go-to market strategy and global advocacy plan.

Bacteriophage and the Physical Structure of the Microbiota

Paul BollykyStanford UniversityStanford, California, United States
Grand Challenges Explorations
Bacteriophage
1 May 2016

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.

Mycobacterium tuberculosis Bacterial Load Assessment by F420 Decay Time Measurement

Warren ZipfelCornell UniversityIthaca, New York, United States
Grand Challenges Explorations
Global Health Solutions
1 May 2016

Warren Zipfel of Cornell University in the U.S. will develop a simple, low-cost method to quantify levels of the tuberculosis-causing bacteria Mycobacterium tuberculosis in different tissues by measuring fluorescence emitted by one of its proteins, F420. To decrease the cost they will use a pulsed laser diode for F420 excitation, and analog electronics to process the fluorescence signal. They will optimize the detection circuitry and optics components, and evaluate its sensitivity and capacity for quantifying the bacteria in sputum and lung tissue. They will also build prototypes of the circuitry coupled to various optical instruments such as a laser-scanning microscope for analyzing extracted samples, and a bronchoscope for inserting into the lungs.

Evaluating the Feasibility and Acceptability of Implementing New Pregnancy Dating and Fetal Growth Standards in Peri-Urban Nairobi

Nick PearsonJacaranda HealthNairobi, Kenya
Grand Challenges
All Children Thriving
25 Apr 2016

Stress Outcomes on Pregnancy, Fetal Growth and Birth Weight: Development of Methods to Identify Mothers at Risk of Preterm Birth and Intrauterine Growth Restriction Resulting from Maternal Stress

Arindam MaitraNational Institute of Biomedical GenomicsKalyani, , India
Grand Challenges India
All Children Thriving
29 Mar 2016

The study aims to assess the effect of depression on pregnancy and develop biomarkers for adverse pregnancy outcomes. It plans to analyze stress outcomes on pregnancy, fetal growth and birth weight. The overall aim of the study is to determine stress biomarkers for early detection of mothers at risk of preterm birth and intrauterine growth restriction (IUGR) and to develop interventions to reduce stress and reduce adverse birth outcomes.

Integrating a Package of Home-Based Early Childhood Interventions into Existing Community Health Worker Protocols in South Africa: A Cluster-Randomized Trial

Denise EvansWits Health Consortium (Proprietary) LimitedSouth Africa
Grand Challenges South Africa
All Children Thriving
22 Mar 2016

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.

Development of a Model for National Scale-up of the Pratt Pouch to Expand Infant Nevirapine Prophylaxis in Uganda, Prevent Mother-to-child Transmission of HIV, and Save Infant Lives

Edward BitarakwateElizabeth Glaser Pediatric AIDS Foundation (EGPAF)Washington, District of Columbia, United States
Grand Challenges for Development
Saving Lives at Birth
16 Mar 2016

The Pratt Pouch, a foilized, polyethylene pouch (similar to a ketchup pouch) designed and proven to safely store NVP doses, offers an innovative way to expand NVP coverage. The Elizabeth Glaser Pediatric AIDS Foundation and its partners propose to introduce and scale up the Pratt Pouch in antenatal care, delivery, and postnatal care services in Uganda. Integrating this technology into existing services will simplify dosing and ensure all HIV-positive women have access to infant NVP. The easy-to-use pouches will empower women to immediately initiate NVP after delivery and encourage them to deliver in a health facility or bring their infants for postnatal care within 14 days.

Low-Cost Technology to assess the Risk of Obstructed Labor in Ethiopia

Rudolph GleasonGeorgia Tech Research CorporationAtlanta, Georgia, United States
Grand Challenges for Development
Saving Lives at Birth
15 Mar 2016

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.

The Simple Absolute Neutrophil Count as a Measure of Mucosal Inflammation and as a Predictor of Linear Growth in Indian Infants

Uma NatchuTranslational Health Science and Technology InstituteFaridabad, , India
Grand Challenges India
All Children Thriving
14 Mar 2016

The proposal attempts to address the lack of a simple, low-cost, prospective biomarker for future short stature or stunting. It aims to validate the use of absolute neutrophil count as a predictor/biomarker for stunting in infants. It has been hypothesized that infants in settings with poor sanitation conditions and associated abnormal inflammation of the gut from infections subsequently have poor absorptions of nutrients and loss of supplements which eventually leads to stunting. Neutrophils are drawn to these sites of microbial colonization or are exhausted during the clearing of microbes from circulation. The study tries to establish the low absolute neutrophil count as a measure of mucosal inflammation and as predictor of linear growth in Indian infants.

Non-Invasive Tuberculosis Diagnosis

Gerard CangelosiUniversity of Washington Foundation, Global WACHSeattle, Washington, United States
Grand Challenges
Global Health Interventions
9 Mar 2016

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.

Creation of a Biorepository and Imaging Data Bank for Accelerating Evidence Generation to Facilitate Children to Thrive

Shinjini BhatnagarTranslational Health Science and Technology InstituteFaridabad, , India
Grand Challenges India
All Children Thriving
7 Mar 2016

The project is aimed at building better bio-banks for long-term storage of bio-specimens. It has been planned to enroll a cohort of pregnant women, who are less than 20 weeks of gestation and follow them until delivery to study their vulnerability to environmental, clinical and biological factors. The study will contribute to our understanding of the association of these various factors with preterm birth (PTB).

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