To improve rural health care for expecting mothers and newborns, Diagnostics For All (DFA) proposes to develop two accurate, low-cost (<$0.10) postage stamp-sized paper-based diagnostics for expecting mothers and newborns that will be used to detect - and enable proper treatment of - (i) anemia and hyper/hypoglycemia and (ii) hypertensive disorders. These point-of-care diagnostics require only a drop of blood or urine and require no additional steps beyond applying the sample. This means that they can be utilized by minimally-trained individuals in communities or clinics in rural settings to prevent unnecessary deaths during pregnancy and childbirth and improve the health of mothers and newborns through early detection of high-risk pregnancies and better patient management.

Partners for Development (PFD) will develop an innovative model to ensure access to ante/postnatal and delivery care (ANC/PNC) in 25 underserved villages in northeastern Cambodia: a transportation system of private sector providers in partnership with local government. To increase demand for such transport and make the system financially sustainable, routes will include schools, markets and other popular destinations in addition to health facilities. Costs will be affordable to consumers and prices adequate for providers via set monthly amounts paid to the providers. In exchange for the monthly payment by the village, the private providers will agree to create affordable transport rates for users. Each village's cost contribution will be calculated according to the distance from its borders to the next stop on the route, reducing the otherwise high cost to the furthermost areas. Families will pay a monthly rate to its respective Village Development Council for unlimited trips, removing what is otherwise a financial disincentive to preventive care. The VDC will then pay each transporter, guaranteeing 24-hour availability. Revolving village loan funds can provide for emergency travel. Villages will: determine optimal routing; establish household fees; set loan interest rates/repayment terms; and determine how to publicize the system. PFD will measure success by: changes in ANC/PNC delivery service utilization; household subscription rates; and transporter profits. The model has replication potential globally.

Baby Monitor, a mobile interactive voice response system, will bring clinical assessment and referrals directly to mothers and their infants in resource-poor settings who are unlikely to access routine care. To date, mobile applications largely have been used to send patient reminders and health information or to collect patient information through intermediaries such as community health workers. Patients in developing countries have not been end-users of mobile diagnostic tools and medical record systems. If successful, this innovation could save lives, improve health outcomes, and optimize the use of extension workers in rural and remote regions where access to health systems is limited and clinical assessment often occurs too late or not at all. Baby Monitor will help mothers to assess the signs and symptoms of newborn and maternal ill-health in the weeks before and after birth. The system will assess responses to verbal screening questions, provide mothers with health information, and, when necessary, make referrals, alert healthcare providers, and dispatch appropriate healthcare workers.

The specific aim of the proposed study is to test the safety and feasibility of a new low-cost device (Odon Device: http://www.youtube.com/watch?v=OGLLXFzULd4) to deliver the fetus during the second stage of labor. This device may be potentially safer and easier to apply than forceps/vacuum extractor for assisted deliveries, and a safe alternative to some Caesarean sections in settings with limited surgical capacity and human resource constraints. It has potential for wide application in resource poor settings even by mid-level providers. If proven safe and effective, the Odon Device will be the first innovation in operative vaginal delivery since the development of forceps centuries ago and vacuum extractor decades ago.

An HIV+ mother will often be reluctant to travel to a clinic the day or two after delivering her baby. She may feel too weak to travel to a clinic miles away or fear stigmatization after explaining why she must go to a clinic after delivering a healthy baby. This leaves millions of children at risk of becoming HIV+ during the birthing process. We have developed and tested in the laboratory a foilized, polyethylene pouch - something like a fast-food ketchup pouch - that can store the medication for months. If the mother is unable to make it to the hospital to deliver, she can tear open the pouch and provide the drugs to the infant, preventing her newborn from becoming HIV+.

Grameen Foundation, in partnership with Ghana Health Service, aims to expand the successfully piloted MOTECH (Mobile Technology for Community Health) initiative to two new districts in a transition plan towards national scale-up. The program will reach approximately 14,000 pregnant women and 46,000 children under five over the two-year implementation, increasing access to accurate health information, generating increased demand for antenatal, postnatal and neonatal care, and providing detailed data on health service delivery and outcomes to Ghana Health Service. MOTECH has two interrelated mobile applications which focus on improving the health of pregnant women and infants in poor rural areas: Mobile Midwife sends targeted, time-specific, evidence-based voice messages containing important health information to pregnant women and new parents in their local language and the Nurse Application allows community health nurses to electronically record care given to patients so they can easily identify clients in their area due for critical care. If a patient misses scheduled antenatal care, the Mobile Midwife service sends a message to remind the woman to go to the clinic. If she fails to attend, her nurse is alerted via text message enabling the nurse to follow up quickly.

This proposal involves testing an innovative fetal heart rate monitor powered by human energy (winner of the global INDEX design award) and mobile phone based mortality audit data to improve timely and appropriate action. Uganda's new national paper-based mortality audit system will be adapted to a mobile phone platform to capture maternal and neonatal deaths and stillbirths, and use this data to improve intrapartum monitoring and response. Facilities will collect this data and will be linked to communities using cell phones to request emergency transport and report births and deaths.

Manish Arora of the GE India Technology Centre Private Limited in Bangalore, India will assess the feasibility of using new low-cost ultrasound transducers to create an affordable diagnostic ultrasound scanner for use in the developing world. Arora's prototype device will also feature a power-saving mode to save battery power, as well as wireless connectivity features that can enable telehealth solutions in remote locations.

Andrew Parfitt of the Institute for Residential Innovation (IResI) in the U.S. will develop a compact, stand-alone device that uses a non-microbial system of progressive reactor modules to mineralize biomass such as sewage and food waste and simultaneously generate electrical power. This system could be used in any location to provide sanitation and purified water for a potable water supply.

Joe Schneider of LAAMScience in the U.S. will develop a reusable and self-decontaminating menstrual napkin that uses photodynamic dyes to inactivate microbial growth on the fabric. The napkin would prevent the need for expensive disposable pads and tampons while offering a hygienic alternative that self-disinfects in the absence of soap or clean water.

Mumtaz Arthur and colleagues of Biofilcom Ltd. in Ghana will develop and field test a prototype toilet facility that incorporates an aerobic digester to decompose waste along with a low-cost microflush valve that uses minimal amounts of wastewater from the washbasins to improve sanitation and user experience. The field tests will help assess and refine cultural, sanitation, and financial aspects of these community facilities. In Phase I, Stephen Mecca of Ghana Sustainable Aid Project in the U.S., along with partners in Ghana, installed and evaluated the performance of three prototypes in Ghana: a 9-stall public toilet, a 3- to 5-stall school toilet, and a 1- to 2-stall family toilet. They demonstrated that the toilet system was effective at removing odors, and isolating and digesting waste, with low associated costs. They also conducted a field survey to evaluate sanitation habits, health and impacts on potential users, and researched ways to improve some of the associated subsystems such as harvesting rainwater for use in the washbasins. In Phase II, Mumtaz Arthur of Biofilcom Ltd. in Ghana will scale up field-testing to an entire village by installing 400 stalls, further research the digestion process, and work to produce a next generation low-cost prototype for local manufacturing, supply, and easy assembly.

Bin Fan of the Research Center for Eco-environmental Sciences in China seeks to develop a decentralized sanitation system which uses a low-cost waterless, vacuum system to collect excrement and kitchen waste. The combined waste can then be processed into organic fertilizer.

Kin-Ping Wong of Retina Pharma, Inc. in the U.S. proposes to test UV-resistant super-water-repellent silica as a coating for toilets, which could reduce the amount of water needed to clean the toilets after use and improve the surface sanitation of the toilets. The silica coating displays the same very high water repellency as the leaves of the lotus flower.

Asafu Maradufu of the University of Eastern Africa, Baraton in Kenya proposes to produce a gel-based disinfectant from plant extracts of Senecio lyratipartitus which can be applied to hands. This disinfectant will reduce contamination associated with the practice of anal ablution among certain communities.

Peter Dreher of Livvon LLC in the U.S. is developing a simple, low-cost toilet for resource-poor settings that uses a hand crank to remove the water from infected feces and urine, and converts the feces into dry, harmless, odorless pellets in a sealed bag that can be used for fertilizer or fuel. The air-tight system will also control odor and keep out flies and vermin, and requires no water, chemicals, or electricity. The system will help to contain human pathogens such as strains of Escherichia coli that cause many diseases and are particularly deadly to small children. In Phase I, they built the toilet and tested it on cow feces, which has similar water and bacteria content to humans. They found that it killed all the pathogens, sealed in odor, and the urine collector made nitrogen fertilizer. In Phase II, they will adapt the design for mass production, and develop a sustainable business model that generates revenue from the fertilizer and from electricity, which will be produced by a feces-fueled generator, to cover the cost of the toilet and collection service. They will also develop a reward system for using the toilets. They will produce several thousand toilets to test their business model in Africa or Haiti, and evaluate the profit or loss.

Kara Nelson of the University of California, Berkeley in the U.S. proposes to disinfect excreta in latrines by converting the ammonia naturally found in urine and feces into a powerful disinfectant by adding an alkalinizing agent to raise the pH level. By killing pathogens immediately and turning excreta into “safe sludge,” all subsequent activities required for excreta management become safer.

Alex Deiters of North Carolina State University in the U.S. will work to discover small molecule inhibitors of short ribonucleic acids (microRNAs) that cause HIV latency in resting T-lymphocytes. Inhibiting the function of these microRNAs could reverse HIV latency, purge HIV reservoirs, and ultimately represent a chemotherapeutic approach to eradicating HIV infection.

Sara Richter of the University of Padua in Italy will develop a therapeutic to completely clear HIV from the body by targeting a proviral DNA structural motif found in both actively and latently infected host cells. In Phase I they analyzed a highly conserved DNA structural motif of four guanine nucleotides (G-4) found in the integrated HIV-1 proviral DNA and found that it regulates proviral transcription and is likely involved in latent infection. In Phase II, they will screen for small compounds that can selectively bind and damage these HIV G-4 structures with the aim to be able to selectively and fully eradicate HIV infection.

Amalio Telenti of the Institute of Microbiology in Switzerland proposes to identify biomarkers specific to HIV latency using high-throughput screening of RNA sequences and a customized screening tool for validating HIV positive individuals. If successful, the biomarkers could be used in the study of HIV latency reservoirs and aid eradication efforts.

Ekaterina Dadachova of the Albert Einstein College of Medicine in the U.S., in collaboration with Arturo Casadevall, proposes to use radioimmunotherapy as a strategy to eliminate HIV-infected cells in patients on anti-retroviral therapy. Targeting viral antigens on these cells with radioactivity-armed antibodies could lead to HIV eradication. This project's Phase I research demonstrated that radioimmunotherapy can kill HIV-infected primary human cells in conjunction with anti-retroviral therapy (ART) and that this antibody can also reach HIV-infected cells in the central nervous system. In Phase II, Dadachova and colleague Joan W. Berman will work with collaborators to study if radioimmunotherapy can kill cells latently infected with HIV, and will also investigate whether eradication of HIV in the central nervous system is an effective and safe modality.

Nicolas Chomont of the Vaccine & Gene Therapy Institute Florida in the U.S. will determine if the stimulation of latently infected cells with HIV antigens is a viable strategy for eradicating the HIV reservoir. If successful, the strategy could be used to cure HIV by combining HAART and immunization with HIV antigens.

Hongxiang Chen of Union Hospital, Tongji Medical College, Huazhong University in China will develop X-ray-sensitive fluorescent nanoparticles conjugated to antibodies that will selectively bind to HIV. Once bound to the targets, the nanoparticles can be excited by X-rays to kill the virus.

Scott Sullivan of the Medical University of South Carolina in the U.S. will build and test a vaginal insert for the prevention of preterm delivery. The device would mechanically support the cervix and dispense medication that would reduce preterm birth risk. It would be inexpensive, small, storage stable, re-usable and easily self-inserted.

James Flanegan of the University of Florida in the U.S. proposes to develop a non-infectious poliovirus vaccine using encapsidated replicons or mature empty capsids that retain full immunogenicity. Either approach can be potentially used to develop a new vaccine that can be safely used in a pre- or post-eradication world.

Lawino Kagumba of ZanaAfrica in Kenya will develop and test sanitary pads that use a locally available agricultural by-product as an alternative low-cost absorbent material. This would enable low-income women and girls to have access to affordable feminine hygiene products, improving their productivity and menstrual health. In Phase I, Lawino Kagumbe and Megan White Mukuria of American Friends of ZanaAfrica Group in the U.S., working with collaborators in Kenya, developed a pulping process that could inexpensively and efficiently process readily available materials into an absorbent pulp suitable for sanitary pads. They also estimated costs of large-scale processing. In Phase II, Kagumba, now working directly for ZanaAfrica in Kenya, will further optimize the manufacturing process, design a plant for large-scale production, and produce low-cost sanitary pads for evaluation by end users in Kenya.

Nick Grassly of Imperial College London and colleagues at CMC-Vellore in India will try to improve the immune response to oral poliovirus vaccine among children in India by treating enteric infections before vaccination. If successful, this simple intervention could reduce the number of vaccine doses required to protect children in lower-income countries.

Melissa J. Moore of the University of Massachusetts Medical School and S. Ananth Karumanchi of Harvard Medical School in the U.S. propose to develop siRNA- based therapies to silence genes in the placenta which produce excess proteins that cause preeclampsia. Temporarily silencing these genes can prolong pregnancy and protect the life of both infant and mother. In Phase I, they demonstrated that siRNAs can be delivered to the placenta, and those designed to target the mouse versions of soluble fms-like tyrosine kinase-1 (sFlt1) could safely decrease protein levels in pregnant mice. In Phase II, Moore, Karumanchi and colleague Anastasia Khvorova will test the safety and efficacy of modified siRNAs for treating preeclampsia in a non-human primate model.

Russell Poulter of the University of Otago in New Zealand will test 'homing' endonucleases found in the genomes of some microbes for their ability to precisely cleave DNA at very specific sites. If successful, these nucleases could be suitable for cleaving and eliminating integrated HIV.

James Blackburn of Southern Illinois University in the U.S. will test a wind turbine-driven sanitation system for its ability to raise and maintain temperatures in an insulated container for the removal of pathogens in human waste. The technology could be used in developing countries in the temperate or equatorial zones to reduce the occurrence of diarrheal diseases.

Mahua Choudhury of University of Colorado in the U.S. will develop a database of epigenetic signatures, changes in DNA and proteins caused by non-genetic factors such as poor nutrition, smoking and environmental contaminants, that could be used as predictors of pre-eclampsia. This information will be used to develop a cost- effective diagnostic tool to detect these markers in blood or urine.

Xiaoyang Wang of University of Gothenburg in Sweden, along with Harvey Cantor of Dana-Farber Cancer Institute in the U.S., will test whether inhibition of a key molecule of inflammation can prevent brain injury in preterm newborns with asphyxia. If successful, this could be used to develop a vaccine-like approach to halt the process of neonatal brain injury.

Margo Klar of the University of Florida in the U.S. will develop a simple and re-usable ceramic device for cutting umbilical cords to reduce the risk of infection in newborns in developing countries. In limited resource settings, cords are often cut with knives or razor blades, which are unsafe and unclean. In Phase I they tested several ceramic-based prototypes on discarded umbilical cords and developed a design that was easy to clean and use, and enabled a simple hygienic cut while reducing potential bacterial exposure. In Phase II, they will optimize the design and perform preliminary tests in a real-life setting in Haiti for safety and ease of use.

Bart Faber of the Biomedical Primate Research Centre in the Netherlands will attempt to create a malaria vaccine using artificial merozoites, which are the blood stage form of the disease. Faber will engineer yeast cells to present multiple surface proteins and measure subsequent antibody production. If successful, this yeast vaccine could be easy to produce and easily transported and stored at ambient temperatures.

Linos Vandekerckhove of the University Hospital Ghent in Belgium proposes to analyze biomarkers and mRNA transcripts to discover well-defined biomarkers that can be used to assess the extent of the latent HIV reservoir in patients with an undetectable viral load.

Christof von Kalle of Deutsches Krebsforschungszentrum/NCT in Germany will study the genomic location and clonal structure of HIV integration sites in host cells. Finding and eliminating these cells could make antiretroviral therapies more effective and increase the survival of infected individuals.

Kristen DeStigter and Brian Garra of Imaging the World in the U.S. will test a newly developed ultrasound imaging and diagnosis system that can be used in rural areas without trained personnel or electricity to help detect critical maternal conditions that increase maternal and infant mortality.

Olufunke Cofie of the International Water Management Institute in Ghana will develop and test fortified fertilizer pellets from treated human excreta for market sale. Production at large scale could enhance agricultural productivity in sub-Saharan Africa, while also contributing to reduction in environmental health risk from untreated human waste. In Phase I Cofie tested several materials that are inexpensive and locally available as binding agents for producing robust fecal sludge pellets suitable for packaging and transportation. She also developed a pelletization unit to produce the pellets, tested their performance as fertilizers, and carried out cost, benefit, and market analyses in Ghana. In Phase II, Cofie and co-investigator Josiane Nikiema will work with partners to establish a supply chain using septic truck operators to scale up production, set up a distribution and sales strategy, and promote the use of their pellets to farmers in Northern Ghana.

Jules Puschett of the TAMUS Health Science Center Research Foundation in the U.S. will study initial evidence that elevated levels of the steroid hormone marinobufagenin (MBG) in urine is a very early indicator of preeclampsia in pregnant women. If true, this common and dangerous condition could be diagnosed early with a simple urine dipstick test, and potentially prevented or treated with a molecule called resibufogenin, which counteracts MBG.

Glenna Bett of SUNY University at Buffalo in the U.S. proposes to develop a device to treat postpartum hemorrhage suitable for use even when medical facilities are absent or minimal, and in non-sterile environments. If successful, this has the potential to reduce perinatal deaths worldwide.

Zhenan Bao of Stanford University in the U.S. will develop a low-cost sensing strip with a diagnostic reader to diagnose pre-eclampsia. The diagnosis is based upon the fact that there is an electrical current change when pre-eclampsia is present. If successful, this diagnostic tool could be used for the early detection and monitoring of this condition to avoid late-stage pregnancy complications.

Adam Spivak from Johns Hopkins University School of Medicine in the U.S. will perform a high-throughput screen to identify novel compounds able to selectively induce cell death in chronically HIV-1 infected cells. Understanding the mechanism of action of such compounds will inform efforts to target and eradicate remaining HIV-1 reservoirs in patients receiving antiretroviral therapy.

Ionita Ghiran of Beth Israel Deaconess Medical Center in the U.S. and collaborator Pierre Striehl of the Harvard School of Dental Medicine propose to develop a cell phone compatible diagnostic screening device based solely on the principles of magnetic levitation, allowing detection of malaria-infected red blood cells. If successful, mass production of the device should be possible due to its construction from basic components.

Qianqian Fang of the Massachusetts General Hospital in the U.S. proposes to develop a portable, low-cost mobile-phone-based near-infrared camera for monitoring brain injury in neonates. If successful, it could help identify and monitor high-risk newborns in resource-limited regions.

Daniel Kavanagh of Massachusetts General Hospital in the U.S. proposes to use a novel class of molecular probes to identify and characterize individual cells latently infected with HIV. If successful, this project will identify new markers that may be used to target and eliminate HIV-infected cells.

Jane Cardosa of Sentinext Therapeutics in Malaysia will design recombinant viruses that can generate self-assembling poliovirus-like particles for use in a poliovirus vaccine. Such a vaccine will be important after wild poliovirus has been eradicated so that people will still have access to a protective vaccine without the necessity of maintaining live poliovirus stocks.

Insu Song and Joachim Diederich of the James Cook University in Singapore propose a cell phone-based system for collecting and analyzing time location-tagged children's crying and breathing sounds to detect respiratory infections. This system provides treatment information for parents and generates public health data regarding the spread of infectious diseases.

David Moss from Lipoxen plc in the United Kingdom aims to develop a non-live polio vaccine using liposomes to entrap and deliver defined poliovirus antigens effectively to the immune system. If successful, the project will expedite the development and global deployment of a simple, economic new polio vaccine.

Yaroslav Ryabov and Denis Broydo of BC Portal, Inc. in the U.S. propose to develop cell phones as biometric identification devices which use the phone camera to take and analyze near-infrared images of hand palms. The unique vein patterns found in the palm can be used by health workers in remote areas to identify individuals and maintain health records for these underserved populations.

Karen Wu of Lucerna, Inc. in the U.S. seeks to develop a portable fluorescence-based device for the rapid detection of procalcitonin (PCT), a biomarker of early sepsis. An inexpensive, simple to use and highly durable device can aid in the early detection of neonatal sepsis, a major cause of infant mortality in developing countries.