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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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Impact of S. Typhi Genome Structure Upon Survival in Water

Gemma LangridgeQuadram Institute BioscienceNorwich, United Kingdom
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Gemma Langridge of Quadram Institute Bioscience in the United Kingdom, along with co-investigators Aaron Jenkins of the University of Sydney in Australia and France Daigle of the University of Montreal in Canada, will collect different isolates of S. Typhi, which causes typhoid fever, to analyze genomic structure, growth, and gene expression to better understand how it can survive at low levels in water, and determine how it can be reactivated for monitoring. Typhoid fever is a potentially fatal disease associated with exposure to contaminated water. S. Typhi, the bacteria causing the disease, exist in water in a so-called viable-but-non-culturable (VBNC) state, which makes it difficult to monitor for control efforts. Their previous analyses have shown that the VBNC bacteria undergo structural rearrangements of their genomes and changes in gene expression, which may explain the reduced growth. They will analyze the correlation between genome structure and growth of different S. Typhi isolates using samples isolated from around 25 typhoid fever cases, and a further 75 stored isolates across the endemic region. Of these, a selection will be tested for their ability to enter a VBNC state and survive in water from areas of high and low typhoid incidence. One isolate that has entered VBNC with a defined structural genotype will be tested to establish the conditions most suitable for resuscitation.

Immonotherapy 'On-the-Go'

Hasan UludagRJH Biosciences Inc.Edmonton, Alberta, Canada
Grand Challenges Explorations
EmergingTechnologies
1 Nov 2019

Hasan Uludag of RJH Biosciences in Canada will develop an affordable immunotherapy system based on genome-integrating transposons that works inside the body for the treatment of a wide variety of diseases such as cancer and diabetes. Emerging immunotherapies offer promising treatment for many diseases, but they require genetic modification of immune cells outside the body, and are thus labor intensive and expensive, limiting their utility in developing countries. They will use engineered nanoparticles in a new approach to immunotherapy that modifies immune cells inside the body. The nanoparticles are derived from polymeric materials that can encapsulate nucleic acids and proteins and release them into host cells. These nanoparticles will be dispersed in a hydrogel matrix with immunostimulatory molecules to create a living bioreactor inside the host that will attract and genetically modify immune cells. They will select polymers for their ability to deliver DNA-based transposons (to facilitate integration into the host genome) to immune cells and to stably express a reporter gene. Optimal polymers will be transferred into mice and they will evaluate transfection efficiency into immune cells with a fluorescent reporter gene. Finally, they will test the therapeutic efficacy of their in situ immune cell engineering approach in a mouse leukemia model.

Improving Vaccination Awareness and Coverage in Somalia (IVACS)

Andrew SealUniversity College London, Institute for Global HealthLondon, United Kingdom
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Andrew Seal of the Institute for Global Health and Development in the United Kingdom will test whether traditional female social groups in Somalia can adopt a participatory learning and action (PLA) approach to improve vaccine knowledge and coverage in humanitarian settings. Vaccine-preventable diseases are prevalent in Somalia; measles is the leading cause of death in children under five, yet less than 40% of children are immunized. This is due in part to lack of knowledge about the benefits of vaccination. The PLA approach is based on the idea that sustainable social change is possible if teachers and learners engage in meaningful dialogue and share ideas and experiences. Abbay-Abbay groups, common throughout Somalia, are social groups of 10-20 women, led by an elected Khalifada (lead woman). They meet regularly and have a core interest in the challenges of child rearing, with most women having direct or indirect experience with losing a child to measles. They will recruit coordinators to support Abbay-Abbay leaders, providing information and facilitating learning around vaccinations. They will evaluate their approach for improving attitudes to vaccination and reducing the incidence of measles via a randomized cluster study.

AI and InfraRed Spectroscopy to Accelerate Malaria Control

Fredros OkumuIfakara Health InstituteIfakara, Tanzania
Grand Challenges Explorations
EmergingTechnologies
1 Nov 2019

Fredos Okumu of the Ifakara Health Institute in Tanzania will develop technology to evaluate mosquito control interventions using a combination of artificial intelligence, infrared spectroscopy, and entomology. Malaria caused over 400,000 deaths in 2017, the majority in the developing world, and an effective way to control the disease is to target the mosquitoes that transmit it. Current tools cannot precisely measure mosquito age or life-expectancy, and are therefore unable to predict the impact of mosquito control interventions. The biochemical composition of the mosquito exoskeleton varies with species and age; as the types of chemical bonds change so does the amount of light absorbed in the mid-infrared region. This can be measured with mid-infrared spectroscopy (MIRS), and they will combine this with machine learning to measure the age of mosquito populations. Using a dataset collected from over 25,000 lab-raised mosquitoes, they have developed a supervised machine learning model that accurately predicts mosquito age and species. They will optimize this model to work also on wild mosquito populations, develop an online platform for real-time analysis of mosquito MIRS data, and test its ability to measure the effectiveness of malaria control interventions.

Monitoring Windborne Activities of Disease Vectors, Pathogens, and Pests

Tovi LehmannNational Institutes of HealthBethesda, Maryland, United States
Grand Challenges Explorations
EmergingTechnologies
1 Nov 2019

Tovi Lehmann of the National Institute of Health in the U.S. will establish cross-country networks of aerial sampling stations in Africa to monitor windborne movement of insects and pests, and evaluate risks to public health, food safety, and ecosystem stability. Vector-borne disease is among Africa's top health priorities, and control of the insect vectors is the primary target for prevention. They will use a unique aerial sampling program to collect airborne insects across Mali and Ghana, and identify insects and pathogens within them by molecular analysis. Sticky nets mounted on helium balloons have shown, in a pilot project, to collect diverse samples, more representative of area fauna than ground sampling protocols. The same project showed that mosquitoes frequently travel (and may spread disease) over hundreds of kilometers. Overnight aerial sampling will be conducted ten nights per month for six months, followed by insect taxonomic identification and RNA/DNA sequencing to identify insects and pathogens. Weather data will be collected from the sampling stations at both ground level and sampling altitude and combined with population data for statistical analysis and simulation of flight patterns. They will produce dynamic, species-specific maps of select insects and pathogens with putative sites of origin, routes and destinations, which will be used to evaluate risks to public health and food security.

S. Typhi Mechanisms of Temperature- and Microbiota-Dependent Environmental Persistence

Denise MonackStanford UniversityStanford, California, United States
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Denise Monack of Stanford University in the U.S. will use a genetic approach to identify the molecular mechanisms that enable the typhoid fever-causing bacterium S. Typhi to survive in aquatic environments and to rapidly adapt to transmission to humans. Annually, S. Typhi causes over 20 million infections and 200,000 deaths, mostly among populations that lack access to clean drinking water. Understanding how S. Typhi persists in water and then quickly adapts to its human host is critical for controlling transmission. Bacteria use various mechanisms to adapt to environmental changes, including so-called RNA thermometers (RNATs), which form secondary structures in mRNAs that can rapidly activate gene expression when temperatures change. They will use their established genetic screening approach to identify new RNATs in S. Typhi and validate their ability to promote bacterial persistence within aquatic microbial communities by generating mutants. They will also follow up on past work in which a bioinformatics approach identified new RNATs that may regulate the expression of the chitinase enzyme, which is used by the cholera-causing bacterium to bind to plankton and create a protective environmental niche. They will evaluate whether chitin is also important for S. Typhi persistence and transmission.

Community Theatre for Immunization

Chijioke KaduruCorona Management SystemsAbuja, Nigeria
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Chijioke Kaduru of Corona Management Systems in Nigeria will use a human-centered approach to develop a community theater production that showcases real stories to educate caregivers on the value of vaccinations and increase childhood vaccine coverage. Almost half of caregivers in Nigeria lack awareness of the value of vaccines, which has increased the incidence of childhood diseases. To address this, they will stimulate social change by showcasing aspects of immunization - identifying concerns and discussing potential solutions - in a community theater production based at the income and education level of caregivers. They will work with stakeholders including immunization teams, community health workers, women's groups, and religious leaders to develop the production. The cast will be made up of community members with real experiences, and performances will be held in public places, traditional meeting spaces, schools, and places of religious worship, and be recorded for future airing. By better engaging caregivers with their human-centered approach, they expect to generate a greater demand for immunization services.

Crowdsourcing to Rebuild Chinese Caregiver Trust in Childhood Vaccines

Joseph TuckerLondon School of Hygiene and Tropical MedicineLondon, United Kingdom
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Joseph Tucker of the London School of Hygiene and Tropical Medicine in the United Kingdom will hold a national crowdsourcing contest to develop a social media-based intervention to improve confidence in childhood vaccines and boost coverage in China. Expert-driven strategies have been launched to promote vaccination coverage in China, but have had limited effect. As an alternative approach, they will apply crowdsourcing to tap into the knowledge of individuals to design a more effective, online intervention. They will open the contest with a call for new ideas that use text, images, and videos to promote vaccinations; enable online evaluation of those ideas by crowd and expert judges; and assemble a steering committee of health experts to produce the finalists. The final content of the intervention will be developed by the finalists in an intensive 'designathon' event. They will test the new intervention in select community health centers in three cities in China and analyze its ability to improve confidence in vaccinations.

Immunization Strategies for Working Mothers

Olukemi AmoduCollege of Medicine, University of IbadanIbadan, Nigeria
Grand Challenges Explorations
Immunization Demand
1 Nov 2019

Olukemi Amodu, Mofeyisara Omobowale and Folakemi Amodu of the University of Ibadan College of Medicine in Nigeria will develop a three-part intervention to provide more convenient and accessible vaccinations for children of working mothers to increase the timeliness and completion of childhood vaccinations. Despite education campaigns, the demand for childhood vaccination in Nigeria is low, partly because working mothers have limited time to attend vaccination clinics. The three-part intervention comprises priority and more convenient immunization services at existing clinics, mobile vaccine clinics for the many mothers who work long hours in the marketplace, and a smartphone-based application to send vaccine reminders. They will test their approach in the city of Ibadan by setting up mobile clinics at three market places to provide weekly vaccination services and education counseling for mothers in their own shops. These mothers will also be supported with a savings program (VaccoSavings) to help them track money saved to pay for vaccines not paid for by the government. They will also enable mothers working in the formal sector to book vaccine appointments at more convenient times at a child welfare center where they will be attended to promptly. All mothers with smartphones will be supported by the VaccApp application to track vaccine schedules and provide automatic reminders. The impact of these combined strategies on the demand for vaccinations will be evaluated after one year.

S. Typhi Survival and Gene Acquisition in Biofilm Communities

Windy TannerUniversity of UtahSalt Lake City, Utah, United States
Grand Challenges Explorations
Salmonella Typhi
1 Nov 2019

Windy Tanner and Jim VanDerslice of the University of Utah in the U.S., together with colleagues from Mehran University of Engineering and Technology in Pakistan, will analyze water samples to determine the conditions that promote the survival of the typhoid fever causing bacterium Salmonella Typhi, and they will use metagenomic deconvolution to identify any gene exchange from other microbial species that may produce drug-resistant strains. S. Typhi is responsible for over 100,000 deaths each year, mostly in the developing world where fecal contamination of food and drinking water is common. The emergence of drug-resistant strains has limited the available treatment options. Biofilms are environmental niches with complex microbial communities and are ubiquitous in the environments where S. Typhi is commonly found. They will sample water and biofilms from a variety of these environments along the fecal-drinking water transmission route in the Sindh province of Pakistan and test for the presence of S. Typhi using qPCR and culture methods. They will also evaluate whether specific organisms stabilize and protect S. Typhi in these biofilms and could cause resistance gene exchange.

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