Apostolos Alissandratos of the Australian National University in Australia will develop a biotechnology platform for the low-cost production of simple, just-add-water diagnostic tests for the early detection of infectious diseases in resource-limited settings. Diagnosis of infectious diseases generally involves detecting pathogen-specific nucleic acids in human samples, which requires unstable reagents, costly procedures, and skilled workers. They have engineered a safe bacterium that produces the biochemical reagents needed to detect the pathogenic nucleic acids as an extract. They will develop a method to freeze-dry this extract so that it is stable at room temperature, simplifying production and storage, and a protocol for incorporating it into a reaction mixture that only requires the addition of water to an individual tube for a diagnostic polymerase chain reaction. They aim to reduce the cost per test by at least 100-fold, and will evaluate their approach for detecting a malaria-causing pathogen.

Bernard Appiah of Texas A&M School of Public Health in the U.S. will produce a one-hour community radio program to be aired twice per week comprising a 10-minute radio drama serial on infant vaccines, a 10-minute panel discussion by community health workers, and a 30-minute phone-in by listeners, to improve on-time childhood vaccinations in Ethiopia. In 2016, on-time and full immunization coverage in Ethiopia was only achieved for 39% of children between one and two years of age, despite long-term efforts to improve it. One of the main reasons for this was lack of communication with mothers about immunizations. To address this, they will harness the popularity of community radio in Ethiopia. They will engage mothers, community health workers, and radio actors to help design a radio drama incorporating relevant topics on childhood immunizations, and train 20 health workers to be part of radio panel discussions. They will air the radio program for six months in two districts, and determine its impact on timely immunization coverage in a selected cohort of mothers with infants.

Rebecca Dempster of HIAS in the U.S. will develop an online game- and mentorship-based intervention to improve the mental health of refugee adolescent mothers in Kenya that integrates into their daily lives and helps them develop new skills. Digital games can help treat mental health disorders such as depression particularly in young people because they have a natural appeal and are easy to access from home. They will recruit ten young mothers, a psychologist, and software programmers to design a mental health game so that it can be used to identify those with mental health disorders and connect them with counselors, and provides interactive challenges to help treat and protect against those disorders as well as build relevant life skills. They will then train these young mothers to act as mentors to support the online game, and pilot test their approach on a sample of 15 refugee adolescent mothers over three months to evaluate feasibility, acceptability, and effect on maternal depression.

Elijah Songok at the Kenya Medical Research Institute hopes to better understand preliminary findings from studies of sex workers that natural resistance to HIV may be linked to genetic markers for type 2 diabetes.

Peter Lillehoj and Chih-Ming Ho of the University of California, Los Angeles in the US. will develop a disposable malaria biosensor based on a SIM card platform. This SIM card-biosensor will allow malaria detection to be performed using a cell phone, making diagnostic testing more widely available in rural and decentralized settings.

Sang-Yeon Cho and Immo Hansen of New Mexico State University in the U.S. seeks to develop a malaria test that measures antibody-antigen reactions through a nanohole to indicate the presence of malaria parasites.

Pushpendra Singh of IIIT Delhi in India will develop interactive training and mentoring sessions for community health workers in India (ASHAs) using mobile phones and interactive voice response systems so they can provide better public healthcare in rural communities. Current training programs are run by medical professionals and require the workers to visit a health center, which may be inconvenient. The lack of medical experts has also reduced the frequency of these programs. These limitations could be overcome with online sessions whereby one expert trains multiple health workers remotely. They have already developed the format of the sessions, which involves an expert delivering a defined curriculum to groups of health workers followed by a question and answer session, and shown that it improved the knowledge and confidence of the health workers in a pilot test. They will now scale up the testing to 500 health workers, and also evaluate the platform as a peer-to-peer learning mechanism for health workers to share their experiences and learn from each other without the need for an expert.

Ellen Vitetta of University of Texas Southwestern Medical Center at Dallas is developing a new vaccine platform that will utilize synthetic B cell epitope mimetics (peptoids) conjugated to protein carriers to make vaccines that will induce robust, specific, and protective antibody responses against pathogens.

Philip J. Shaw of Thailand's National Center for Genetic Engineering and Biotechnology will seek to identify potential drug targets and vaccine antigens in the malaria parasite using a novel technology to reduce specific gene expression. By fusing a natural genetic “riboswitch” onto gene targets, the team will attempt to attenuate gene expression and thereby determine gene function.

Miguel Prudencio of Instituto de Medicina Molecular in Portugal will test the theory that modified live rodent malaria parasites (P. berghei) can be used in a vaccine to elicit a strong immune response in humans without being able to infect human red blood cells and cause illness. This was successfully tested in Phase I, and they also established that the human antigens carried by the parasites could induce a selective immune response in mice. In Phase II, they will test their vaccine in Phase I/IIa human trials and evaluate it for safety, tolerability, and immunogenicity. They will also extend their approach to another human malaria parasite P. vivax, and begin optimizing methods for large-scale vaccine production.

Kuan-Teh Jeang of the National Institutes of Health in the U.S. will investigate whether cells infected by one virus become resistant to infection from other viruses, and if this viral interference can confer protection against HIV. The team will develop an attenuated virus to test whether over-expression of viral envelope proteins within cells can confer resistance to further HIV infection.

Vijay Pancholi of The Ohio State University Research Foundation in the U.S. will attempt to attenuate the S. pneumonia bacteria by altering export of the GAPDH enzyme, a function thought to be essential to the bacteria's survival. Preventing export of this key enzyme will decrease bacterial virulence, allowing the attenuated strain to be used for development an affordable live vaccine for pneumococcal pneumonia.

Anders Hakansson of the University of Buffalo in the U.S. has identified a protein from human breast milk (Human Alpha Lactalbumin Made Lethal to Tumor cell, or HAMLET), that kills respiratory tract bacteria. Hakansson will attempt to understand the mechanism by which HAMLET binds to and kills pheumococci without the bacteria developing resistance.

Renjie Chang of Lavax in the U.S. will develop and test a vaginal suppository that uses a strain of commensal bacteria which has the ability to immobilize sperm and capture viruses. If successful, the bacteria could be used as a reversible contraceptive that also affords protection against viruses such as HIV and herpes.

Dr. Ryan Lilien of the University of Toronto in Canada will work to computationally model the structural and functional effects of point mutations on a target protein's active site. With the development of predictive models of pathogen evolution and the spread of resistance, this information can be used to guide drug development and optimization.

Because Leishmania is transmitted to humans when sand flies feed on humans, Jesus Valenzuela of the National Institutes of Health in the U.S. proposes to develop a novel vaccine against salivary proteins of sand flies with the aim to induce a strong immune response against the parasite.

Jasper Ogwal-Okeng of Makerere University in Uganda will test whether the insect-eating plants can reduce the population of mosquitoes and their larvae. Ogwal- Okeng will study optimal numbers and placement of such plants and record subsequent impact on mosquito and larvae populations to further refine this vector control method.

Abhijit Das of Arogya Medtech Pvt. Ltd. in India will develop a device - CEREBROS - that is a modular unit combining electroencephalography (EEG) and near infrared spectroscopy (NIRS) together with an Internet of Things (IoT) component incorporating a telemonitoring platform. This system enables continuous remote monitoring of cerebral hypoxia and seizures and early detection and management of hypoxic ischemic encephalopathy (HIE) at point-of-care. The device is in the form of a wearable cap for neonates. It will also include a multivariate classifier incorporating quantitative EEG metrics and cerebral oximetry metrics, which will identify disease-specific patterns that can be presented remotely by a neonatologist simultaneously in voice, text, pictures, or video or animations. The device could be provided, through both public and private care providers, under an affordable rental or pay-per-use model. The device provides an easy-to-use alternative to structural imaging (CT or MRI) that has better sensitivity and specificity, especially for neonates or infants less than 2 years old.

Guozhi Wang of the National Institute for Control Pharmaceutical & Biological Products in China will assess the effectiveness of a new inexpensive skin test that can differentiate between true Tuberculosis infection and the markers of the BCG vaccination. Because the current TB screening protocol is not sensitive enough to tell the difference, this new test could lead to earlier and better treatment options for those with early-stage infections.

Kevin Plaxco of the University of California, Santa Barbara, United States seeks to develop a diagnostics platform based upon measuring the electric current produced by the binding of antibodies to DNA molecules. If successful, this method will provide a rapid, single-step reagent free measurement of immune antibodies which could significantly augment disease detection and vaccine validation efforts.

HIV has a very high rate of mutation allowing it to very rapidly develop resistance to AIDS therapies. The essential viral enzyme, HIV reverse transcriptase, lacks a "proofreading" or "repair activity" leading to errors or mutations. Karen Anderson of Yale University is working on "stealth" compounds that have a unique anchor specific for HIV. These compounds encourage the virus to make mutations until the virus is annihilated.

Enterotoxigenic Escherichia coli (ETEC) cause diarrhea by producing two distinct enterotoxins that attack intestinal cells. Adrienne Paton and colleagues at the University of Adelaide in Australia propose to develop a harmless probiotic bacterium capable of binding and neutralizing both these enterotoxins by mimicking their respective receptors, thereby preventing disease.

Hans Brunner of Value Spring Technology, Inc. in the U.S. will build and test an artificial intelligence (AI) tutor to teach the scientific method and critical thinking skills to individual students at their pace and level. All children learn differently but one-on-one lessons are often prohibitively expensive or unavailable. To address this, in collaboration with two non-profit teaching institutions, they will adapt their AI software for education, and build and train an AI tutor, Ali. Ali will be designed to produce natural sounding language to engage students in conversation involving open-ended questions and answers that stimulate critical thinking, which is based on the Socratic method. Students will be taught at their own pace and level of understanding, and Ali will be built to ensure each topic is fully understood before starting the next. They will engage teachers to test and critique their AI tutor approach and to evaluate its teaching performance.

Manish Bhardwaj of Innovators in Health in India will build a social networking platform consisting of voice messages accessed via mobile phone that is monitored by community health workers to connect small groups of young pregnant women and new mothers in India. Currently, community health workers provide home visits to help adolescent mothers combat mental health disorders. However, their capacity is limited. An additional difficulty for adolescent mothers is the lack of social networks caused by moving to new neighborhoods to live with their husbands. Social networks can protect against mental health disorders by providing peer support and the relevant knowledge and experience to overcome any challenges. They will trial their approach in a rural area in India and recruit young mothers with no access to mental health care into specified social groups. Each group will be associated with trained community health workers who provide additional support to the mothers, and manage the messages and posts.

Ross Boyce at the University of North Carolina in the U.S. will develop an approach that uses new methods of mapping households together with available health data to better identify places that have limited access to healthcare to improve immunization coverage. Many sub-Saharan African countries have very poor rates of childhood vaccination coverage. Improving coverage requires identifying those households and areas with poor access to healthcare, but this is challenging with the limited data available. To more accurately measure healthcare access and thereby immunization coverage, they will perform a six-month study in a rural sub-county of western Uganda. By providing user-friendly tools to health workers and providers, they will generate more accurate household maps and assess three different metrics of healthcare access using freely available software and a Bayesian statistical framework. They will evaluate the accuracy of their approach for predicting coverage by conducting a cross-sectional survey to determine the vaccination status of all children aged between 12 and 23 months in the sub-county.

Laser light at a specific setting can activate antigen presenting cells in the skin and temporarily make cellular membranes permeable. Mei X. Wu and colleagues at Massachusetts General Hospital/Harvard Medical School in the U.S. will test whether injection of a vaccine into laser-exposed skin can significantly enhance immune responses stimulated by the vaccine.

Olaf Kutsch of the University of Alabama proposes that HIV latency is controlled by host-gene promoter interference, a mechanism that prevents the initiation of viral gene expression. Understanding how host-gene promoter interference controls latent HIV-1 infection may aid development of therapies to deplete latent HIV in patients.

Mosquito transmitted pathogens such as dengue and malaria are a significant disease burden on the world's population. Paul Young of the University of Queensland in Australia aims to develop a novel vaccine approach that is based on blocking mosquito transmission of these disease agents rather than inducing pathogen- specific immunity.

Michael Leibowitz of the UMDNJ-Robert Wood Johnson Medical School in the U.S. will investigate whether malaria parasites bind to, invade and replicate in the endothelial cells that line the blood vessels to test the theory that endothelial cells play an important role in the development of malaria infection and may serve as undiscovered reservoirs for parasite latency.

Gérrard Poinern of Murdoch University in Australia will develop and test an implantable subcutaneous device made from same calcium mineral that bones are made of, which will release contraceptive drugs in a sustained and controlled way for a period of months. Creating of this device uses ultrasound and microwave technology, allowing for eventual low-cost manufacture in developing countries.

Owain Millington and Gail McConnell of University of Strathclyde in the United Kingdom seek to adapt existing imaging systems to provide non-invasive in vivo imaging of Leishmania parasites present in macrophages and dendritic cells, and then use a targeted laser to destroy them. They will also test the hypothesis that targeting these cells for destruction will stimulate protective immunity against future Leishmania parasite infections.

A3G, protein found in human cells that inactivates several viruses including HIV, is "switched off" in proliferating T cells. Harold Smith of the University of Rochester will screen for small molecule compounds that bind to A3G in cells and turn its anti-viral activity back on.

Gerald R. Smith of the Fred Hutchinson Cancer Research Center in the U.S. seeks to identify inhibitors of a bacterial DNA repair enzyme that allows tuberculosis to mutate. Identifying these inhibitors could lead to therapies that kill bacteria and limit drug resistance.

Pandelakis Koni of the Medical College of Georgia will study the complex sugar coating that surrounds and protects HIV to see if parts of this shield can serve as targets for a vaccine, to generate antibodies that bind to and accelerate the killing of HIV-infected cells.

The project will study the genetic material from environmental samples from humans (healthy and ill), cattle and their meat to estimate the proportion of E. coli and K. pneumoniae in the microbiome. The main objective is to better understand the distribution of bacteria and its resistance genes, Escherichia coli and Klebsiella pneumoniae bacteria and extended spectrum beta-lactamase (EsβL) and carbapenemases encoding genes in distinct ecological sources.

Lena Hulden of the University of Helsinki in Finland will test the hypothesis that saliva from newly emerging mosquitoes activates dormant P. vivax parasites in the liver. By robust statistical analysis of the timing of P. vivax outbreaks, as well as molecular analysis of mosquito saliva, Hulden hopes to eventually identify the trigger for these relapses in hopes of controlling outbreaks.

Aims to access all 68.3 million living births certificates from Brazil, from 1994 to 2016, and compare them with breastfeeding policies in all Brazilian hospitals to assess the impact of the initiatives on infant health. The study also plans to estimate the number of avoidable deaths during this time period, if those initiatives were adopted in Brazil.

The Augmented Infant Resuscitator (AIR) empowers health workers to achieve and maintain effective ventilation. It provides intuitive real-time, actionable feedback to birth attendants during ventilation. With [email protected] funding, the team will complete the Product Realization Process (PRP) in partnership with Philips Healthcare vital for the global commercialization of the AIR training device. The team will demonstrate resultant impact on skills acquisition, retention and newborn outcomes.

Vojo Deretic of the University of New Mexico in the U.S. proposed that autophagy, a process by which cells destroy cellular components and intracellular pathogens, can be induced through drug therapy to not only destroy the HIV virus in infected cells, but also to block its transmission from dendritic cells to T cells. This project's Phase I research demonstrated that autophagy can destroy HIV, block dendritic to T cell transfer of HIV, and promote antigen presentation by dendritic cells. In Phase II, Deretic's team will screen for compounds that can induce autophagy to block HIV from infecting cells, limit HIV spread, and enhance dendritic cell immune functions.

Luiz Ozaki and Gail E. Christie of Virginia Commonwealth University in the U.S. will genetically engineer bacterial viruses to carry peptides that block the development of the malaria parasites, survive in the mosquito gut, and spread through vector populations. If successful, these bacteriophages could be used as “gene dissemination tools” for effective control of the malaria.

In this proposal, INMED will directly address the gaps in jaundice management by introducing the Bilikit, a comprehensive package of screening (Jaundice Ruler), quantitative diagnostic (Bilistick®) and phototherapy treatment (Bili-Hut™) innovations appropriate for the resource-constrained context. The goal will to be improve diagnostic and treatment capacity at downstream hospitals to avert treatment delay. CHAs will be trained to screen infants to better inform referral decisions.

Peter Ngure of Daystar University in Kenya seeks to develop a biological control for sandflies using fungi found in the local soil in Kenya. These entomopathogenic fungi, which attach like parasites onto adult insects and larvae and kill them, will be harvested and cultured to isolate virulent strains that can eradicate sandflies, which are responsible for the spread of visceral leishmaniasis.

Bruce Grieve of Manchester University in the United Kingdom will develop a low-cost, stereo-printed sensor that mimics plant leaves and stems and can detect and signal the presence of live pathogens as an early warning system to help protect crops in low-resource settings. They will demonstrate proof-of-concept of their approach in the laboratory by designing three dimensional sensors with specific patterns of cells and chemically-doped polymers to identify an ideal surface on which pathogenic fungal spores can grow and differentiate. Incorporated sensor cells will be designed to detect the live pathogens and produce a detectable response, such as a visible density change, and results can be stored locally or transmitted wirelessly. They will test different sensor designs for the detection of rust pathogens in wheat. Their approach can be adapted to detect multiple pathogens simultaneously, including viruses, as well as for human and livestock pathogens, and when deployed in the field can ultimately be linked to national surveillance systems.

To interrupt reproduction of the malaria parasite in the mosquito gut, Greg Garcia and Sheetij Dutta of Walter Reed Army Institute of Research seek to identify and block a gametocyte stage receptor for xanthreunic acid, which is known to trigger the differentiation of gametocytes, an essential step in the life-cycle of the malaria parasite.

David Anderson of the Macfarlane Burnet Institute for Medical Research in Australia will develop a low-cost, simple to use, sample collection device to improve sample quality and ensure accurate and timely diagnosis in remote, low-resource areas. Obtaining high quality serum samples needed for diagnosing a variety of diseases is challenging in these regions due to the lack of equipment and expertise to process the samples and stabilize them for transport to the diagnostic laboratories. They have developed a device comprising an integrated two-step process based on lateral flow chromatography that separates plasma from other blood cells and dries it on paper so it can be stably transported. The dried plasma samples can also be used directly in the laboratory, which accelerates analysis. They will modify the device to separate and store larger volumes of plasma using 25 healthy volunteers, and test its performance for diagnosing patients with different infections, including Hepatitis B and C, compared with fresh plasma.

Yen Verhoeven of the Paragon Learning Research Group in the U.S. will create a digital platform for massive open online courses (MOOCs) and a supportive online community of professionals for kindergarten to sixth grade teachers to transform their teaching practices and bring STEM and 21^st century skills to their schools. MOOCs were developed as a means to provide free education to everyone. However, their content is typically restricted to videos and reading with little interactive learning, which is inadequate for teaching life skills such as critical thinking and creativity. And encouraging teachers to adopt new teaching practices requires additional professional support from peers and mentors. To address these issues, they will work with teachers and teaching experts to formulate a new MOOC design containing a variety of instructional resources and free professional development classes and develop a beta version of the online community platform. They will evaluate the course by teaching it to local K-6 teachers and gathering feedback to refine the content.

Joanna Busza of the London School of Hygiene and Tropical Medicine in the United Kingdom will help vulnerable young mothers who sell sex in Zimbabwe by involving them in designing self-help groups incorporating virtual meetings via social media to build support networks and teach them life skills such as money management and parenting. Adolescent sex workers who become mothers are at high risk of developing mental health problems such as anxiety and depression, and often have little support caring for their children. They will involve adolescent women in the design stage by holding interviews and group discussions to gather opinion on social media and group meetings, as well as identify the types of skills they most need and how best to teach them. They will train peer educators to lead six-month virtual support groups and recruit young, pregnant sex workers to pilot test the approach in two urban sites in Zimbabwe.

Tatiana Salisbury of King's College London in the United Kingdom along with colleagues at the Royal College of Art in the United Kingdom and the Manhiça Health Research Centre in Mozambique will develop a strategy to improve the mental health of young mothers in Mozambique by adapting existing technology-based and group-based methods to teach them life skills such as parenting and social skills. Almost half of Mozambican girls have had a baby by the time they are 18 years old. Together with associated events including being excluded from school and family conflicts, this can damage their mental health and lead to suicide. They will recruit experts in mental and maternal health and implementation science, analyze resources and local infrastructure, and, together with young mothers, their families, and other stakeholders, co-develop the skill-strengthening and delivery methods. Delivery methods to be analyzed include text messaging, mobile phone applications, and group meetings. They will then pilot test their strategy with three different delivery methods using up to 60 pregnant and young mothers (aged 15-24 years) over four months, and evaluate their effect on mental health.

Daniel Fletcher of the University of California, Berkeley in the U.S. will develop a microscope that attaches to cell phones to capture high-contrast fluorescent images of malaria parasites. Custom software on the phone will automatically count the parasite load, with results and patient information wirelessly transmitted to clinical centers for tracking.