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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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Inhaled Oxytocin: Bringing Gold Standard Postpartum Hemorrhage Prevention to Women in Greatest Need

Victoria OliverMonash UniversityClayton, Victoria, Australia
Grand Challenges for Development
Saving Lives at Birth
19 Dec 2016

This project seeks to substantially expand access to oxytocin through the development of an affordable, simple to administer inhaled oxytocin delivery system. Using innovative technology, inhaled oxytocin is formulated as a fine powder that can withstand the climatic conditions common in tropical regions without the need for refrigeration. The product therefore removes the requirement for cold chain supply and storage, potentially allows task-shifting to lower tier healthcare and community workers and has the potential to save 146,000 lives over 8 years.

Evaluating the Approach to Administration and Dose of Bovine Lactoferrin to Prevent Neonatal Infections in Low Birthweight Newborns in Pakistan

Michael DibleyThe University of SydneySydney, New South Wales, Australia
Grand Challenges for Development
Saving Lives at Birth
19 Dec 2016

The goal of this project is to improve newborn survival among low birth weight (LBW) infants through a daily prophylactic dose of bovine lactoferrin (bLF). A two-stage project will be conducted with formative research followed by randomized controlled trial (RCT) to evaluate the appropriate daily dose of bLF and its efficacy in preventing neonatal infections.

Development and Evaluation of the RELI Delivery System - An Innovative, Simplified, Low-Cost Infusion Pump for Obstetric and Newborn Emergencies

Mike EisensteinProgram for Appropriate Technology in Health (PATH)Seattle, Washington, United States
Grand Challenges for Development
Saving Lives at Birth
6 Dec 2016

PATH's novel infusion pump, the RELI Delivery System, was designed to address many of the barriers surrounding access to infusion pumps in LRS: it does not require electricity or a battery, is inexpensive to manufacture and operate, does not require expensive consumables, and has a simple user interface. We will develop a functional prototype and related job aids to share with stakeholders.

Outpatient Treatment of Neonatal Sepsis by the Rectal Administration of Gentamicin

David McAdamsProgram for Appropriate Technology in Health (PATH)Seattle, Washington, United States
Grand Challenges for Development
Saving Lives at Birth
6 Dec 2016

We propose to investigate the feasibility of a needle-free method of administration for the antibiotic gentamicin via the rectal route. Under this project we would conduct laboratory release studies, preclinical rectal bioavailability studies and stakeholder interviews to assess the feasibility of novel concept. This delivery method would improve access to outpatient treatment of neonatal sepsis in areas serviced by low level healthcare providers and would remove the inherent risks associated with parenteral delivery.

Field Validation of a New Protein-To-Creatinine (PrCr) Strip Test: An Impactful New Tool to Improve Diagnosis of Preeclampsia at the Front Lines of Antenatal Care in Low-Resource Settings

Nicole AdvaniProgram for Appropriate Technology in Health (PATH)Seattle, Washington, United States
Grand Challenges for Development
Saving Lives at Birth
1 Dec 2016

PATH seeks to improve access to improved preeclampsia screening in routine antenatal care (ANC) by addressing the need for a low-cost, accurate proteinuria screening tool to replace the protein-only dipstick as the standard used in routine ANC in LRS. PATH is working in collaboration with LifeAssay Diagnostics, Ltd. (South Africa) to develop and support validation of a simple, low-cost protein-to-creatinine ratiometric urine dipstick test and is seeking to demonstrate the feasibility for implementation and use of the test within routine ANC.

ELICIT: Early Life Interventions for Childhood Growth and Development in Tanzania

Estomih MdumaHaydom Lutheran HospitalHaydom Mbulu, Tanzania
Grand Challenges
All Children Thriving
30 Nov 2016

Microarray Patch for Delivery of a Combination of Antibiotics for the Treatment of Neonatal Sepsis

Mary KearneyQueen's University BelfastBelfast, United Kingdom
Grand Challenges for Development
Saving Lives at Birth
30 Nov 2016

This team proposes to develop and test an innovative microarray patch to deliver a combination of antibiotics for the treatment of neonatal sepsis. An easy-to-use, less-invasive, affordable delivery method for amoxicillin and gentamicin could expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period.

Safer Deliveries Using Point-of-Care Decision Support and Monitoring

Marc MitchellD-Tree InternationalWeston, Massachusetts, United States
Grand Challenges for Development
Saving Lives at Birth
29 Nov 2016

The Safer Deliveries project will improve the ability of nurses and midwives to identify danger signs for a woman and her baby during the critical period of labor and delivery and link these measures to specific decision support rules that guide the health worker in taking corrective action. Using ultra-low-cost disposable ECG leads, D-tree International will build a phone based device that provides continuous tracking of fetal and maternal heart rate and uterine contractions during labor and delivery leading to more timely and effective interventions to save the life of the mother and infant.

Life-saving Instruction for Emergencies (LIFE) Delivered Using Serious Games and mHealth Technologies

Mike EnglishUniversity of OxfordOxford, United Kingdom
Grand Challenges for Development
Saving Lives at Birth
29 Nov 2016

Drawing on 10 years of experience developing and delivering essential newborn care training, this project will develop 3D games using an iterative co-design process in UK and Kenya so it excites users and addresses needs and preferences. This project will explore incentives for learning and develop data capture tools to understand who is playing as well as where and when they are playing. This project will also design a test of the effectiveness of our training in Kenya, explore how to extend the approach to maternal care and plan for dissemination and testing.

Testing and Implementation of Low-cost Breathing Aid for Infants in Tigray, Ethiopia

Anjelica GonzalezYale UniversityNew Haven, Connecticut, United States
Grand Challenges for Development
Saving Lives at Birth
29 Nov 2016

PremieBreathe has built a functional infant breathing aid for $450, one tenth the price of commercial models. The device, a humidified high flow nasal cannula (HHFNC), is the gold standard of non-invasive neonatal respiratory care in high-income countries. With the support of Saving Lives at Birth, PremieBreathe will conduct initial trials at Ayder Referral Hospital in the Tigray region of Ethiopia, and identify design, manufacturing, and distribution partners to prepare for scaled production and dissemination.

Structural-Based Design of HIV Vaccine Targeting the Native Conformation of Neutralizing Epitopes in gp41 MPER

Ling YeEmory UniversityAtlanta, Georgia, United States
Grand Challenges China
China - New Interventions
28 Nov 2016

Ling Ye of Emory University in the U.S., working with Lu Lu of Shanghai Medical College, Fudan University in China, will design a potent HIV vaccine using selected sequences of one of the virus's envelope proteins to trigger the production of broadly neutralizing antibodies. This has been problematic due to the diversity of the viral envelope glycoprotein and its glycosylation shield which prevent the immune system from recognizing it. The membrane-proximal external region (MPER) of the viral envelope protein has been identified as an attractive target for inducing neutralizing antibodies and they have fused it with another viral protein to form a chimera that can partly neutralize infection. They will build on this result by modifying the structure of the MPER to stabilize it in a more active conformation and by fusing it with slightly different viral proteins that can then be immunized altogether. They will evaluate whether this vaccine strategy further stimulates broadly neutralizing antibody production and can fully neutralize HIV in several animal models.

Structural-Based Design of HIV Vaccine Targeting the Native Conformation of Neutralizing Epitopes in gp41 MPER

Lu LuFudan UniversityShanghai, China
Grand Challenges China
China - New Interventions
28 Nov 2016

Lu Lu of Shanghai Medical College, Fudan University in China working with Ling Ye of Emory University in the U.S., will design a potent HIV vaccine using selected sequences of one of the virus's envelope proteins to trigger the production of broadly neutralizing antibodies. This has been problematic due to the diversity of the viral envelope glycoprotein and its glycosylation shield, which prevent the immune system from recognizing it. The membrane-proximal external region (MPER) of the viral envelope protein has been identified as an attractive target for inducing neutralizing antibodies, and they have fused it with another viral protein to form a chimera that can partly neutralize infection. They will build on this result by modifying the structure of the MPER to stabilize it in a more active conformation, and by fusing it with slightly different viral proteins that can then be immunized altogether. They will evaluate whether this vaccine strategy further stimulates broadly neutralizing antibody production and can fully neutralize HIV in several animal models.

Development of a Cost-Effective Automated Vaccine Manufacturing System Combining Vero Cell Lines High-Density Bioreactor and High-Performance Membrane Purification Platform in a Self-Contained Miniaturized Facility

José CastilloUnivercellsBrussels, Belgium
Grand Challenges
Vaccine Manufacturing
23 Nov 2016

José Castillo of Univercells in Belgium will create a compact low-cost and automated vaccine manufacturing platform by integrating three new technologies to produce more affordable vaccines at around 0.15USD per dose. Vaccine doses are generally 1-10USD most of which is due to inefficient production and high manufacturing costs including the need for major infrastructure. This relatively high cost prohibits their widespread use particularly in developing countries with limited funds. Starting with an inactivated poliovirus vaccine they will design and develop a compact high cell density bioreactor that concentrates vaccine production and high affinity capture membranes to streamline purification. They will house the technologies in a compact series of isolators that can be accommodated in a smaller laboratory space and perform pilot testing at a manufacturer's site to evaluate productivity and analyze purity and concentration of the vaccine.

An Intergenerational Prebiotic Approach to Establishment of a Healthy Colonic Microbiome in Infants

Balakrishnan RamakrishnaSRM Institutes for Medical ScienceChennai, , India
Grand Challenges India
All Children Thriving
21 Nov 2016

The study intends to develop an inter-generational intervention to ameliorate neonatal gut microbiota. It is based on the hypothesis that consuming prebiotic starches such as high amylose maize starch (HAMS) by mothers during the third trimester of pregnancy will modify their fecal microbiota and will subsequently lead to a beneficial variation in the fecal microbiota of the newborn infant. This will consequently guide favorable intestinal activity, thus enhancing growth, and intellectual competence of the infant in the intermediate and long term.

Ultra Low-cost Transferable Automated (ULTRA) Platform for Vaccine Manufacturing

Tarit MukhopadhyayUniversity College LondonLondon, United Kingdom
Grand Challenges
Vaccine Manufacturing
18 Nov 2016

Tarit Mukhopadhyay of University College London in the United Kingdom will develop a manufacturing platform to reduce the production costs of recombinant protein vaccines. Current manufacturing procedures involve serial batch operations in large complex facilities requiring highly trained operators and extensive testing and are inefficient and costly. They will build a platform that integrates and automates key steps to reduce labor costs and capital expenditure and improves product design and control procedures to reduce quality control requirements. Their aim is to maximize the number of doses with the minimal starting material leading to recombinant subunit vaccines at 0.15USD per dose rather than the current costs of several USD per dose. They will develop their approach initially using a rotavirus vaccine candidate.

The Maternity Episode of Care Prototype (Liberia)

Sarah ScheeningOpen Development, LLCWashington, District of Columbia, United States
Grand Challenges for Development
Saving Lives at Birth
16 Nov 2016

This project will build and test a prototype application that streamlines and automates patient, provider and payer transactions across the maternal/newborn EOC. The goal is to pilot the application in Liberia, where the government must overcome operational challenges to engage private providers in the Liberia Health Equity Fund.

Segmented Filamentous Bacteria as a Vaccination Platform to Protect Young Children Against Enteric Pathogens

Pamela SchnupfParis Descartes UniversityParis, France
Grand Challenges
Global Health Interventions
15 Nov 2016

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.

An Affordable and Robust Diagnostic Platform for Neonates and Young Children in Low-Resource Settings

Rashed ShahSave the Children Federation, IncWestport, Connecticut, United States
Grand Challenges for Development
Saving Lives at Birth
15 Nov 2016

Save the Children proposes an affordable and exclusive point-of-care diagnostic device for accurate measurement and interpretation of key vital signs (oxygen saturation, respiratory rate and temperature) among young infants (0-59 days) and children (2-59 months). It is equipped with a unique universal pulse oximeter sensor. The device will improve the quality of pneumonia case management and possible serious bacterial infections at community and health facility levels in low-resource settings.

Using Biomarkers to Predict TB Treatment Duration

Qian GaoFudan UniversityShanghai, China
Grand Challenges China
China - New Interventions
14 Nov 2016

Qian Gao of Shanghai Medical College Fudan University in China, working with Clif Barry of The National Institute of Allergy and Infectious Diseases in the U.S., will support a clinical trial to shorten the treatment time for tuberculosis (TB) from six months to four months by helping to identify predictive biomarkers in individuals that only require the shorter treatment. Shortening treatment when possible will substantially reduce costs and the emergence of drug resistance which is a major barrier to eradicating this deadly disease. The phase 2b clinical trial will recruit 620 TB patients at multiple clinics in South Africa and China who will be monitored for disease burden by PET/CT scans and diagnostic assays during treatment and will supply blood and sputum samples for testing. He will analyze RNA and inflammatory markers in serum samples from the Chinese trial participants to identify more robust biomarkers for predicting shorter treatments. He will also determine the strains of the causative Mycobacterium tuberculosis the source of any reinfection (relapse or new infection) and the presence of drug resistant bacteria in these patients and how these link with treatment duration and disease outcome.

Using Biomarkers to Predict TB Treatment Duration

Clif BarryNational Institute of Allergy and Infectious DiseasesBethesda, Maryland, United States
Grand Challenges China
China - New Interventions
14 Nov 2016

Clif Barry of The National Institute of Allergy and Infectious Diseases in the U.S., working with Qian Gao of Shanghai Medical College Fudan University in China, will support a clinical trial to shorten the treatment time for tuberculosis (TB) from six months to four months by helping to identify predictive biomarkers in individuals that only require the shorter treatment. Shortening treatment when possible will substantially reduce costs and the emergence of drug resistance, which is a major barrier to eradicating this deadly disease. The phase 2b clinical trial will recruit 620 TB patients at multiple clinics in South Africa and China who will be monitored for disease burden by PET/CT scans and diagnostic assays during treatment, and will supply blood and sputum samples for testing. He will analyze RNA and inflammatory markers in serum samples from the Chinese trial participants to identify more robust biomarkers for predicting shorter treatments. He will also determine the strains of the causative Mycobacterium tuberculosis, the source of any reinfection (relapse or new infection), and the presence of drug resistant bacteria in these patients, and how these link with treatment duration and disease outcome.

Validation Study of an Electricity-free Oxygen Concentrator in Western Uganda.

Roger RassoolUniversity of MelbourneMelbourne, Victoria, Australia
Grand Challenges for Development
Saving Lives at Birth
9 Nov 2016

One of the reasons oxygen therapy is not reaching the many thousands of babies and children it could save is due to the fact that electricity is not always available in small health facilities. To address this problem, this team has successfully developed FREO2, an electricity-free oxygen concentrator which runs on the energy from water flowing in a nearby stream, and which requires no fuel. This project will enable a major field trial in a health center in Western Uganda, where the design for this innovation will be refined in close collaboration with the health workers.

An Accurate, Rugged and Low-Power Syringe Pump for Maternity and Neonatal Care in Resource Limited Settings

Maria OdenRice UniversityHouston, Texas, United States
Grand Challenges for Development
Saving Lives at Birth
9 Nov 2016

There is international consensus that syringe pumps are an essential medical device to support care of mothers and newborns at district hospitals. Yet, they are often unavailable in low-resource settings because of high cost, technical complexity, and lack of brand name consumables. The project's idea is to scale AutoSyp, a low cost, low power, syringe pump in maternity and neonatal wards of hospitals in Malawi.

Dissolvable Microneedle Manufacturing Platform Technology: Two-Dose Thermostable IPV Patch

Michael SchraderVaxess Technologies Inc.Boston, Massachusetts, United States
Grand Challenges
Vaccine Manufacturing
7 Nov 2016

Michael Schrader of Vaxess Technologies Inc. in the U.S. will develop a microneedle patch that stabilizes vaccines and can deliver multiple doses through the skin at defined times thereby reducing cost waste and the need for repeat immunizations. Vaccinations delivered intradermally via microneedles are at least as effective as intramuscular delivery via injection but reduce the requirement for needles and trained health workers. The patch uses a silk fibroin protein that protects the vaccine against high temperatures removing the need for cold storage and controls the timing of release through the skin. They will refine the material for delivering two doses of inactivated poliovirus vaccine evaluate its safety and activity in animal models and optimize the manufacturing process to ensure reduced costs.

Reversible Contraceptives that Block Primordial Follicles

Patricia DonahoeMassachusetts General HospitalBoston, Massachusetts, United States
Grand Challenges Explorations
Contraceptive Discovery
1 Nov 2016

Patricia Donahoe and David Pepin of Massachusetts General Hospital in the U.S. are using a cell-based screening platform to develop a new class of hormonal contraceptive that works at the early stage of primordial follicle activation to prolong the contraceptive effect and reduce side effects, thereby promoting wider use particularly in the developing world. This early stage of follicle development in the ovary is suppressed by a hormone (Mullerian inhibiting substance or MIS) to regulate egg production. They considered that a drug that could mimic MIS could completely suppress ovulation and act as a powerful contraceptive. In contrast, most available hormonal contraceptives work once ovulation has begun, thereby requiring daily dosage, and share unwanted side effects including migraine and increased risk of some diseases. In Phase I, they designed a luciferase-based screening platform using engineered mammalian cells and screened 5,500 compounds from which they validated three candidate contraceptive compounds with high specificity and activity and limited toxicity. In Phase II, they will adapt their assay for higher throughput screening and screen 100,000 compounds to identify diverse classes of molecules for evaluation as ovarian suppressants. The contraceptive efficacy of validated candidates with favorable properties will then be tested in mice.

Gene Knockdown System for Cryptosporidium

William WitolaUniversity of Illinois at Urbana-ChampaignUrbana, Illinois, United States
Grand Challenges Explorations
Cryptosporidium Infection
1 Nov 2016

William Witola of the University of Illinois in the U.S. will help develop new drugs for treating children infected with the protozoa Cryptosporidium by using a gene knockdown approach to evaluate candidate drug targets. Found in contaminated water, Cryptosporidium is the second most common cause of potentially lethal diarrhea in young children in developing countries. There are no safe and effective drugs available due largely to the lack of genetic tools for studying Cryptosporidium in the laboratory. Phosphorodiamidate morpholino oligomers (PPMOs) are small molecules that can be designed to bind and silence specific genes also in protozoa. If these genes encode for proteins critical for vital cellular functions, the PPMOs can cause death. To evaluate his approach, he will design PPMOs and test their ability to silence essential Cryptosporidium genes and thereby block chronic infection in mice.

A Novel Platform for Screening Non-Hormonal Contraceptives

Jianjun SunUniversity of ConnecticutStorrs, Connecticut, United States
Grand Challenges Explorations
Contraceptive Discovery
1 Nov 2016

Jianjun Sun of the University of Connecticut in the U.S. is developing non-hormonal contraceptives using a fly-based ovulation assay to identify compounds that specifically block the rupture of follicles, which is required to release eggs for fertilization also in mammals. The popular female contraceptive "pill" alters the hormonal cycle and is widely used throughout the Western world. However, it can have undesirable side effects. In Phase I, they developed a medium-throughput follicle rupture assay using Drosophila follicles and showed that three out of four drugs inhibiting Drosophila follicle rupture had the same effect in mice. They discovered that these drugs also inhibited the production of superoxide, which promotes follicle rupture. Building on this new knowledge, in Phase II, they will develop a high-throughput luminescence-based superoxide-detection assay in Drosophila and screen 13,000 compounds. Top hits will again be validated for activity also in mice, and they will further identify their cellular mechanisms of action using available genetic tools in Drosophila.

A Next-Generation Pipeline to Discover Male Contraceptives

Martin MatzukBaylor College of MedicineHouston, Texas, United States
Grand Challenges Explorations
Contraceptive Discovery
1 Nov 2016

Martin Matzuk, along with Nicholas Simmons of Baylor College of Medicine in the U.S. and Masahito Ikawa of Osaka University in Japan, will build a male contraceptive drug discovery platform comprising a library of two billion small compounds generated by DNA-Encoded Chemistry Technology (DEC-Tec) at relatively low cost, and a panel of male-specific fertility proteins. Contraception options for men are currently limited to condoms or vasectomy. A safe, low-cost small molecule contraceptive similar to the female "pill", could also help men to better control family planning. They are using the CRISPR/Cas9 mutagenesis strategy to identify new genes essential for male fertility in mice. For ten of these new genes, they will synthesize the corresponding fertility proteins and test them for binding to the compounds in their new, expanded DNA-tagged drug library.

Cryptosporidium Culturing and Drug-Screening

Anastasios TsaousisUniversity of KentCanterbury, United Kingdom
Grand Challenges Explorations
Cryptosporidium Infection
1 Nov 2016

Anastasios Tsaousis of the University of Kent in the United Kingdom will build a screening platform to identify drugs that can be used to treat diarrhea caused by the parasite Cryptosporidium, which is the second major cause of death in children under five years old in developing countries. There are currently no effective drugs for treating Cryptosporidium, largely because it cannot easily be grown in the laboratory making it difficult to study and test for new drugs. They have developed a two-dimensional cell culture system using a specific cell type that can be stably infected with Cryptosporidium and cultivated long term. They will use the CRISPR/Cas9 gene modification technique to alter selected Cryptosporidium genes for monitoring parasite growth, and use it in their cell culture system to screen a library of FDA-approved drugs to identify candidate drugs that block Cryptosporidium growth.

Preferences for Contraceptives in Botswana

Paul Crits-ChristophUniversity of PennsylvaniaPhiladelphia, Pennsylvania, United States
Grand Challenges Explorations
Family Planning
1 Nov 2016

Paul Crits-Christoph and Chelsea Morroni of the University of Pennsylvania in the U.S. will develop a mobile phone application that enables women to identify the method of contraception best suited to their needs to help reduce the number of unwanted pregnancies in Botswana, which is currently estimated at 44%. Although around 61% of women are reported to not want any more children, the most commonly used contraceptives are single use, such as condoms, despite the availability of longer-term measures like intrauterine devices. They will work together with individuals in Botswana to compile a list of 10-20 attributes valued by women in a contraceptive, such as duration of protection and ease of use, and program existing software to identify a woman's preferred choice using a simple series of questions. The application will then be used to test their hypothesis that the method of contraception most suited to an individual is different to that being prescribed by health workers in Botswana.

A Multidimensional Approach to Family Planning Needs

Jane HarriesUniversity of Cape TownCape Town, , South Africa
Grand Challenges Explorations
Family Planning
1 Nov 2016

Jane Harries of the University of Cape Town in South Africa will take a multisensory approach to increase the use of contraception, particularly over the long term, across South Africa. By exploring how different contraceptives are perceived via multiple senses, not only visual perceptions but also how they feel, and how their use impacts the daily life of the woman, and her wider network, they hope to identify new barriers that influence uptake. They will present a range of contraceptives to 150 women and 50 men, and encourage them to take photographs and make drawings as a way to explore their different perspectives on the contraceptives and on family planning in general. Group discussions and individual interviews will also be held to further evaluate how people react to the contraceptives, and how they affect their lives.

Rabbit as an Animal Model of Pediatric Cryptosporidiosis

Xun SuoChina Agricultural UniversityBeijing, China
Grand Challenges Explorations
Cryptosporidium Infection
1 Nov 2016

Xun Suo of China Agricultural University in China will develop a rabbit model of cryptosporidiosis that mimics the human disease, which presents as severe diarrhea particularly in young children, to help identify new treatments. Current animal models of infection by the parasite Cryptosporidium are suboptimal: mice are not naturally infected, while pigs and calves can be infected but are expensive and more difficult to manage, and none show the same symptoms as humans. Rabbits are naturally infected by Cryptosporidium and display human-related symptoms. They are also practical to handle and breed, and are relatively inexpensive. They will isolate infective oocysts from diseased rabbits in the wild, and establish the infection in the laboratory. They will also devise protocols to evaluate the disease such as scoring the severity of symptoms, and sequencing the parasite strains. The value of their model as a screening platform for identifying new drugs will also be tested.

A Method for Assessing the Reservoirs of Antibiotic Resistance Genes

Howard OchmanUniversity of TexasAustin, Texas, United States
Grand Challenges Explorations
Drug Resistance Burden
1 Nov 2016

Howard Ochman of the University of Texas in the U.S. will develop an approach to identify bacteria that can spread antibiotic resistance genes to other bacteria and harm human health. Most methods for monitoring antibiotic resistance are used once resistance has occurred. Here they will measure the capacity for developing resistance, which should help better evaluate how antibiotic resistance persists, spreads and circulates on a global scale. They will develop a simple method based on a single-cell technology to link a marker rRNA gene, for classifying the bacterial species, with a gene known to confer antibiotic resistance. They will use this method to identify antibiotic resistance gene-carrying bacteria within microbial communities comprising trillions of cells, and analyze how it spreads through a mixed bacterial population.

Assessment of Contraceptive Needs of Unmarried Men

Marion Sumari-de BoerKilimanjaro Clinical Research InstituteMoshi, Tanzania
Grand Challenges Explorations
Family Planning
1 Nov 2016

Marion Sumari-de Boer and Kennedy Ngowi from Kilimanjaro Clinical Research Institute in the United Republic of Tanzania and Rosalijn Both from Segel Research and Training Consulting in Ethiopia will use mobile phones to learn about the contraceptive needs and behaviors of young unmarried men in Ethiopia and Tanzania in order to promote the use of contraception. This group is mostly overlooked in studies aiming to improve contraceptive and family planning practices, even though their behavior is directly relevant. They will recruit a diverse group of men aged between 18 and 29 years old and collect data by sending them weekly SMS messages containing specific questions. They will also conduct regular interviews and group discussions to identify contraceptive practices and needs.

Understanding the Power of Men's Social Networks

Paul FlemingUniversity of Michigan, School of Public HealthAnn Arbor, Michigan, United States
Grand Challenges Explorations
Family Planning
1 Nov 2016

Paul Fleming of the University of Michigan School of Public Health along with Jay Silverman and Holly Shakya at the University of California, San Diego Center for Gender Equity and Health in the U.S. will learn about the social networks of husbands of adolescent girls in Niger, and how these networks influence decisions to use of family planning. The study will be conducted in collaboration with Pathfinder International, building on their Reaching Married Adolescents program. Niger has the highest fertility rate in the world, and men usually control all decisions on use and type of contraception. However, it is unclear how and why they make these decisions, and particularly how other men in their lives influence these decisions. They will conduct in-depth interviews with a group of 20 husbands of adolescent girls in Niger, and characterize the social networks of a further 300 such men. They will also interview key members of these social networks to determine their views on these husbands’ of adolescent girls use of contraception. Together, they hope to identify social barriers and, ultimately, effective models for increasing use of family planning to improve the health of married adolescent girls.

Building on Accepted Tools for Malaria Elimination

Edward ThomsenLiverpool School of Tropical MedicineLiverpool, United Kingdom
Grand Challenges Explorations
Malaria Analytics
1 Nov 2016

Edward Thomsen of the Liverpool School of Tropical Medicine in the United Kingdom will build an open-source software platform tailored to support efforts to eliminate malaria by amalgamating desirable features from two existing disease data management platforms. The Disease Data Management System (DDMS) is an existing platform that integrates multiple datasets and supports operational decision-making through unique functionality such as automated outbreak alerts. In contrast, the District Health Information Software 2 (DHIS2) is a well-established platform that is the preferred solution for managing aggregated and individual case data. It has a large user-base and powerful analytics interface. They will develop software to modify DHIS2 with the desired features of DDMS and evaluate the performance of their integrated platform over one year in a malaria control program in Zambia.

Development of An Automated Early Warning System for Malaria

Kathryn ColbornUniversity of Colorado DenverAurora, Colorado, United States
Grand Challenges Explorations
Malaria Analytics
1 Nov 2016

Kathryn Colborn of University of Colorado Denver in the U.S. will develop a statistical model to predict future outbreaks of malaria and help identify the most effective intervention strategy. Current models can help work out where and why malaria outbreaks occur rather than predicting future outbreaks. They will use supervised machine learning to develop a set of predictive algorithms using available data including weather, demographics, and malaria incidence in children under five years old from Mozambique. From this set, the best algorithm for predicting malaria will be selected by cross validation on an independent dataset, and subsequently tested in the field using monthly malaria case reports.

Establishing Anti-Cryptosporidial Drug Pharmacokinetic/Pharmacodynamic Relationships

Samuel ArnoldUniversity of WashingtonSeattle, Washington, United States
Grand Challenges Explorations
Cryptosporidium Infection
1 Nov 2016

Samuel Arnold of the University of Washington in the U.S. will develop methods to evaluate drug candidates for treating Cryptosporidium infections, which cause severe diarrhea particularly in young children from developing countries. There are no effective drugs against the Cryptosporidium parasite. This is partly because when it infects humans it becomes isolated in specific cells lining the gastrointestinal tract, which is where a drug would also need to be located at sufficient concentrations to be effective. However, the standard in vitro models are unable to easily and rapidly predict the efficacy of multiple drug candidates at this specific location. To address this, they will build a cell model of the intestinal wall that can also be infected with Cryptosporidium, and measure the permeability of a panel of protein kinase inhibitors that they have developed to kill the parasites. They will also use the software platform Gastroplus that can simulate the behavior of a drug once it has been administered and predict concentrations at multiple sites in the gastrointestinal tract. They will evaluate their method for predicting drug activity in vivo by testing the drugs in a neonatal mouse model of Cryptosporidium infection.

A Bioengineered Model of Human Intestinal Cryptosporidiosis

Honorine WardTufts Medical CenterBoston, Massachusetts, United States
Grand Challenges Explorations
Cryptosporidium Infection
1 Nov 2016

Honorine Ward of Tufts Medical Center in the U.S. will develop a three-dimensional model of the human intestine for rapid screening of drugs targeting the parasite Cryptosporidium, which causes potentially lethal diarrhea in young children in developing countries. Developing drugs against Cryptosporidium has been particularly difficult, partly because of the limited understanding of the parasites behavior in the human intestine, and particularly of the effect of malnutrition, which commonly co-occurs with infection and likely contributes to disease severity. They will build a three-dimensional model of the human intestine using a scaffold of silk proteins and a hollow lumen structure lined with cells derived from human intestinal stem cells supported by underlying human myelofibroblasts. They will infect their cell model with fluorescently labelled Cryptosporidium to evaluate how the parasite affects the intestine, and to determine its capacity for high-throughput drug screens.

The Use of Routine Collected Data to Define Disease Importation and Target Intervention

Thomas ChurcherImperial College LondonLondon, United Kingdom
Grand Challenges Explorations
Malaria Analytics
1 Nov 2016

Thomas Churcher of Imperial College London in the United Kingdom will develop an analytical method to more accurately determine the origin of new cases of malaria in regions with low levels of the disease, which is critical for elimination efforts. Current methods are unreliable as there are no standardized criteria and they often rely solely on interviews. They will use routinely collected travel history data and disease maps to develop rigorous methods for estimating whether a case of malaria is either acquired locally or imported from another region. The accuracy of their method will be tested by comparing it with available data from Swaziland.

Development of a Novel Organ-On-Chip of the Endometrium

Kevin OsteenVanderbilt University Medical CenterNashville, Tennessee, United States
Grand Challenges Explorations
Contraceptive Discovery
1 Nov 2016

Kevin Osteen of Vanderbilt University Medical Center in the U.S. will develop a three-dimensional cell model that mimics the interior of the human uterus (endometrium), which consists of several different cell types and a vascular system, that can be used to discover new contraceptives and therapeutics. They will build a microfluidics device with three chambers, one to support primary endometrial cells from human donors and immune cells, one with stromal fibroblasts, and finally an extracellular matrix chamber. The fabricated EndoChip will be evaluated by measuring it's ability to mimic endometrial functions such as remodeling in preparation for pregnancy.

Metrics for Public-Health Perspective Surveillance of Bacterial Antibiotic Resistance

Olga Tosas AuguetUniversity of OxfordOxford, United Kingdom
Grand Challenges Explorations
Drug Resistance Burden
1 Nov 2016

Olga Tosas Auguet of the University of Oxford and collaborators at the Modernising Medical Microbiology Consortium, Guy's and St Thomas' NHS Foundation Trust, Oxford Genomics Centre and London School of Hygiene and Tropical Medicine in the United Kingdom, and Oxford Tropical Network Overseas Programs in southeast Asia and Africa, will develop a new approach for the large-scale surveillance of bacterial antibiotic resistance in low-income settings. Current methods mainly involve the collection and analysis of individual clinical samples, which requires diagnostic equipment often unavailable in developing countries. They will pool together ~300 samples of rectal swabs and stools taken from biobanks, and analyze each pool by shotgun sequencing to identify the abundance of bacterial species and antibiotic resistance genes. They will use these data to calculate resistance potential and to determine how accurately this metric approximates the numbers of infections in a population that are resistant to a specific antibiotic.

Family Planning Needs of South African Adolescent Girls

Jennifer BrownUniversity of CincinnatiCincinnati, Ohio, United States
Grand Challenges Explorations
Family Planning
1 Nov 2016

Jennifer Brown of the University of Cincinnati in the U.S. will apply cultural consensus modeling (CCM) to identify cultural factors that affect contraceptive practices among South African adolescent girls aged between 14 and 17. This demographic currently has one of the highest rates of unwanted pregnancies and sexually transmitted infections (STIs). However, there is limited empirical data on the underlying reasons, particularly related to the use of so-called dual contraceptives, which protect against both pregnancy and STIs. The CCM approach involves a series of questions and interviews designed to identify factors that individuals believe influences the use of contraceptives within their group as a whole, rather than themselves individually. This will help identify cultural barriers that limit the use of contraceptives. They will test their approach using around 300 girls in South Africa and evaluate how these perceived factors are associated with actual contraceptive practices.

Development of a Novel Humanized Microbiome Mouse Model for Cryptosporidiosis

Jan MeadEmory UniversityAtlanta, Georgia, United States
Grand Challenges Explorations
Cryptosporidium Infection
1 Nov 2016

Jan Mead of Emory University in the U.S. will develop a mouse model of cryptosporidiosis using human fecal transplants to mimic changes in the bacterial populations (microbiome) in the gut that occur in the human disease, which causes substantial morbidity and mortality in young children from developing countries. Drugs used to eradicate the intestinal parasite Cryptosporidium are thought to be affected by the levels and types of bacteria that populate the human gut, which is of particular importance in malnourished children who most often become infected. They will colonize germ-free mice with human fecal material and infect them with Cryptosporidium. The effect of the infection and of selected drugs on the microbiome will then be evaluated by DNA sequencing.

Targeting Motility and the Acrosome for Contraceptive Drugs

Andrew HopkinsUniversity of DundeeDundee, United Kingdom
Grand Challenges Explorations
Contraceptive Discovery
1 Nov 2016

Andrew Hopkins of the University of Dundee in the United Kingdom is developing a screening platform using live human sperm to identify new male contraceptive drugs that inhibit two separate activities required for fertilization, namely motility and formation of the acrosome on the head of sperm cells. Currently, the only effective, widely available, and reversible form of male contraception is the condom, which has limited appeal. Alternative male contraceptives are needed to help reduce the estimated 89 million unintended pregnancies each year. In Phase I, they successfully developed a high-throughput screening platform incorporating confocal microscopy and phenotypic analysis tools optimized for 384-well culture plates for automated screening of large numbers of candidate male contraceptive compounds. In Phase II, Christopher Barratt also of the University of Dundee, will further the development of new contraceptives by studying the properties and mechanism of action of the hits identified in Phase I and perform additional screens with both focused and diverse compound libraries.

A Spatiotemporal Recommendation Engine for Malaria Control

Brian ReichNorth Carolina State UniversityRaleigh, North Carolina, United States
Grand Challenges Explorations
Malaria Analytics
1 Nov 2016

Brian Reich of North Carolina State University in the U.S. will develop a software model to measure the risk of local malaria outbreaks in real-time in the Democratic Republic of Congo and identify treatment strategies for control efforts to more effectively allocate their limited resources. They will build this "recommendation engine" using demographic health survey data from household surveys on disease incidence and types of treatment used, and devise a simple mathematical formula that calculates priority scores, defined by user-specified risk factors, for different regions, which can be easily interpreted by stakeholders.

Point-of-Collection Silica-Coating and Preservation of Stool

Kenneth StedmanPortland State UniversityPortland, Oregon, United States
Grand Challenges Explorations
Global Health Solutions
1 Nov 2016

Kenneth Stedman of Portland State University in the U.S. will test a low-cost and simple method for simultaneously collecting and stabilizing stool samples that can be used for diagnosing helminth infections in remote locations. The samples allow quantification of eggs from the helminth parasite, which causes intestinal infections that are endemic in many developing regions, and will help monitor large-scale treatment efforts. The method is based on his vaccine-stabilization technology, which was developed along with James Laidler at Portland State University.

Using Game-Based Learning for Assessing Behaviors and Needs

Elmar StroomerDesign without Borders Uganda Ltd.Kampala, Uganda
Grand Challenges Explorations
Family Planning
1 Nov 2016

Elmar Stroomer of Design without Borders Uganda Ltd. in Uganda will develop an interactive game combining methods from game-based learning to collect data on decisions made around family planning in Uganda. These data can then be used to develop strategies that encourage effective family planning for individuals and communities. They will recruit participants to co-create the game to simulate real-life situations using a human-centered design process. This includes interviews and role-playing sessions to identify the contexts in which family planning decisions are made to ultimately gain a deeper understanding of what influences them. The methods help motivate people to change their behaviour by involving them in the design process and enabling them to experience the consequences of certain choices. They will pilot their game-based learning concept on 5 to 8 groups and develop a manual to guide participants and assessors.

A Physiological Mouse Model for Cryptosporidiosis

Boris StriepenUniversity of GeorgiaAthens, Georgia, United States
Grand Challenges Explorations
Cryptosporidium Infection
1 Nov 2016

Boris Striepen of the University of Georgia in the U.S. will develop a new, more natural mouse model for cryptosporidiosis, which is a leading cause of severe diarrhea in children, to help identify effective treatments. Unlike previous mouse models of this disease, these mice do not need to be immune deficient as they can be infected by a natural strain of the Cryptosporidium parasite, which they previous isolated from house mice. They will genetically modify this strain so it will fluoresce and can thus be easily located in the mice and within individual cells. These mice also experience symptoms more similar to the human disease, and they will use it to assess the effects of malnutrition, which often co-occurs with infection and appears to worsen symptoms. They will also study the effect of different bacterial communities in the gut on disease progression and the effects of existing and emerging treatments.

Silencing Genes to Identify New Targets for Drug Development

Alejandro Castellanos-GonzalezThe University of Texas Medical Branch at GalvestonGalveston, Texas, United States
Grand Challenges Explorations
Cryptosporidium Infection
1 Nov 2016

Alejandro Castellanos-Gonzalez of the University of Texas Medical Branch in the U.S. will use their gene silencing approach involving premade complexes of protein and small RNA to identify drug targets in the Cryptosporidium parasite, which causes severe diarrhea in young children in developing countries. Their gene silencing method involves synthesizing the so-called argonaute protein that is able to cut a single gene and attaching it to a single-strand antisense RNA that is designed to target a specific gene. This method can be easily scaled up for high-throughput drug target screens. They identified 100 candidate genes that are likely to be essential for the parasite to function and are not similar to genes found in humans, making them potentially suitable as targets for drugs. They will determine whether these genes can be fully silenced using their approach, and for 20 candidate targets evaluate the effect of silencing on parasite infection in cultured cells.

Validation of Baboon Infant Cryptosporidium Infection Model

Ngalla JillaniInstitute of Primate ResearchNairobi, Kenya
Grand Challenges Explorations
Cryptosporidium Infection
1 Nov 2016

Ngalla Jillani of the Institute of Primate Research in Kenya will build an infectious infant baboon model of cryptosporidiosis that mimics the disease in human infants under two years old to help identify new treatments. Childhood Cryptosporidium infections are common in developing countries and cause substantial morbidity and mortality. Current models in small animals fail to fully recapitulate the course of infection and disease symptoms in humans, making them less valuable for studying the disease and identifying effective treatments. They will inoculate small groups of infant baboons with different doses of a strain of Cryptosporidium that naturally infects these animals, and evaluate disease manifestation.

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